Iodine-Mediated Cyclization of Enamines to Imidazole-4-Carboxylic Derivatives with Sequential Removal of Nitrogen Atoms from TMSN3

Article abstract of DOI:10.1021/acs.joc.1c01145

An iodine-mediated oxidative [4+1] cyclization of enamines with TMSN3 for the synthesis of 2,5-disubstituted imidazole-4-carboxylic derivatives has been developed. The mechanistic studies revealed that the reaction proceeds through a sequential removal of two nitrogen atoms from TMSN3. The synthetic utility was further demonstrated with a gram-scale reaction and various derivatization transformations of the products.

Full text of DOI:10.1021/acs.joc.1c01145

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Article
Iodine-Mediated Cyclization of Enamines to Imidazole-4-Carboxylic
Derivatives with Sequential Removal of Nitrogen Atoms from TMSN3
Peng Gao,* Huaijuan Chen, Zi-Jing Bai, Sheng Zhang, Mi-Na Zhao, Desuo Yang, Yingchun Li,
Jiangwei Zhang, and Xiaomei Wang
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ABSTRACT: An iodine-mediated oxidative [4+1] cyclization of
enamines with TMSN3 for the synthesis of 2,5-disubstituted
imidazole-4-carboxylic derivatives has been developed. The
mechanistic studies revealed that the reaction proceeds through a
sequential removal of two nitrogen atoms from TMSN3. The
synthetic utility was further demonstrated with a gram-scale
reaction and various derivatization transformations of the products.
interest in developing novel methods for the synthesis of
heterocycles,11 herein, we report an iodine-mediated oxidative
[4+1] cyclization of enamines with a sequential removal of two
nitrogen atoms from TMSN3 (Scheme 1b).
INTRODUCTION
■
Azides are important and versatile reagents in organic
chemistry, particularly in the construction of functional
nitrogen-containing molecules.1,2 Among these reactions, the
decomposition of azides to incorporate one nitrogen atom into
the functional molecules is typically rationalized by extrusion
of dinitrogen or diazo compounds to give amines,3 amides,4
amidines,5 or N-containing heterocycles6,7 (Scheme 1a).
Imidazoles are privileged scaffolds in a variety of biologically
active molecules and valuable synthetic building blocks (Figure
1).12 Especially, the derivatives of 2,5-disubstituted imidazole-
4-carboxylic acids are of continuing interest in drug discovery
because many of them show vital activities on a large number
of biological targets,13 such as the inhibitor of mPGES-1,13a
antiallergic13b and antituberculosis agents,13c inhibitor of
allosteric B-Raf protein kinase,13d and antagonist of CCK2
receptor.13e Consequently, much effort has been devoted to
the synthesis of this skeleton. The synthetic approaches to 2,5-
disubstituted imidazole-4-carboxylic derivatives include multi-
step synthesis via condensation/substitution/cyclization,14
transition-metal-catalyzed crossing-coupling based on available
imidazoles,15 or related variations of these reactions.16 While
effective, these methods suffer from limitations such as the use
of prefunctionalized starting materials, requiring toxic tran-
sition metal catalysts, and finally, poor functional group
compatibility. Recently, the synthesis of 2,5-disubstituted
imidazole-4-carboxylic derivatives was further improved via
oxidative cyclization of enamine compounds.6a Sharada
reported a PIFA-mediated cycloaminative approach providing
polysubstituted imidazoles via in situ generation of 3° enamino
esters from aliphatic amines and acetylenedicarboxylate
Scheme 1. Reactions of the Decomposition of Azides to
Remove Two Nitrogen Atoms
Different mechanisms may be operative in these aminations
that involve transition metals catalysis,2a radical chemistry,1c or
nitrene intermediates.1d A variety of classic methods have been
established via this pathway, including the Curtius rearrange-
ment,2b Schmidt reaction,7 Staudinger reaction,2c et al., as well
as the application in pharmaceutical chemistry,8 materials
science,9 and biotechnology.10 However, to the best of our
knowledge, exceptions of this denitrogenative reaction of
azides have been rarely described. Because of the significance
of azides in organic synthesis and in continuation of our
Received: May 17, 2021
Published: July 26, 2021
https://doi.org/10.1021/acs.joc.1c01145
J. Org. Chem. 2021, 86, 10492−10500
© 2021 American Chemical Society
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Figure 1. Representative 2,5-disubstituted imidazole-4-carboxylic derivatives.
esters.6a Yu has developed a Cu-catalyzed cyclization of
trifluoromethyl-substituted enaminoesters with TMSN3 as
the nitrogen source to prepare the imidazole compounds.6b
However, because of the requirement of multiple electron-
deficient groups (such as −CO2R, −CF3) on the substrates to
reduce the byproducts, the reported systems are inefficient for
the similar cyclization of the more general enamine
compounds. Therefore, the exploration of novel and practical
methods for the construction of 2,5-disubstituted imidazole-4-
carboxylic derivatives is still highly desirable and of great
significance.
a
Table 1. Optimization of the Reaction Conditions
entry
base, ratio
Na2CO3
K2CO3
NaOAc
solvent
yield (%)
13
1
2
3
4
5
6
7
8
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
EtOAc
DME
CH3CN
DMSO
DMF
DMF
DMF
DMF
DMF
DMF
b
39
b
66
b
31
b
K2CO3/NaOAc, 2.5:1
K2CO3/NaOAc, 3:1
K2CO3/KOAc, 3:1
Na2CO3/NaOAc, 3:1
Cs2CO3/NaOAc, 3:1
NaOH/NaOAc, 3:1
K2CO3/NaOAc, 3:1
K2CO3/NaOAc, 3:1
K2CO3/NaOAc, 3:1
K2CO3/NaOAc, 3:1
K2CO3/NaOAc, 3:1
K2CO3/NaOAc, 3:1
K2CO3/NaOAc, 3:1
K2CO3/NaOAc, 3:1
K2CO3/NaOAc, 3:1
K2CO3/NaOAc, 3:1
72
RESULTS AND DISCUSSIONS
■
85
78
77
66
47
68
42
67
66
Initially, N-benzyl β-enamino ester 1a and TMSN3 were
reacted in the presence of I2 in N,N-dimethylformamide
(DMF) at 80 °C for 12 h, providing the methyl-2,5-diphenyl
1H-imidazole-4-carboxylate 2a in 13% yield (Table 1, entry 1).
This result encouraged us to further optimize the reaction
conditions. A screening of bases with different combinations
and loadings showed that the addition of a base could enhance
the reaction outcomes (Table 1, entries 2−10). The results
revealed that the combination of K2CO3 and NaOAc was more
effective, delivering product 2a in 85% yield (Table 1, entry 6).
Solvents such as EtOAc, 1,2-dimethoxyethane (DME), and
dimethyl sulfoxide (DMSO) gave inferior results (Table 1,
entries 11−14), which also indicated that DMF is a better
choice for this transformation. In the absence of I2, no desired
9
10
11
12
13
14
15
16
17
18
19
20
c
0
d
79
e
75
f
56
g
68
h
67
a
product 2a was observed (Table 1, entry 15). A further
Reaction conditions: 1a (0.3 mmol), TMSN3 (0.9 mmol), I2 (0.9
b
increase or decrease in the loading of I2 did not help to
improve the outcome of the reaction (Table 1, entries 16 and
17). Lowering the temperature to 60 °C led to a drop in the
product yield (Table 1, entry18). The yield was decreased to
68% when NaN3 was used as the nitrogen source (Table 1,
entry 19). This might be due to the poor solubility of the
inorganic salt in the reaction mixture. We then tried to reduce
the reaction time; however, 2a was obtained only in 67% for 6
h (entry 20).
Having established the optimized conditions, we aimed to
define the substrate scope of this method. First, the reactivity
of different N-benzyl β-enaminoesters was examined. As seen
in Scheme 2, the substrates with different substituents on the
phenyl ring, including electron-donating (−Me, −OMe) and
electron-withdrawing groups (−F, −Cl, −Br, −CF3), pro-
ceeded smoothly to afford the corresponding products (2a−
mmol), base (4 equiv) in solvent (6 mL) at 80 °C for 12 h. 3.5 equiv
c
d
e
base was used. I2 was not used. 2.5 equiv of I2 was used. 3.5 equiv
f
g
h
of I2 was used. 60 °C. NaN3 was used instead of TMSN3. 6 h.
m). In most cases, moderate to good yields of the desired
products were obtained. The lower yield of 2d might be due to
the steric effect of the o-methyl group. Heterocyclic variants of
substituted imidazole-4-carboxylic esters 2n (2-thienyl) and 2o
(3-thienyl) could be accessed in 67% and 74% yields,
respectively. In addition, bi- and fused aryl N-benzyl β-
enaminoesters were also compatible, delivering the desired
products in moderate yields (2p and 2q). Further inves-
tigations on the ester group showed that 1r bearing a −CO2Et
group was also a suitable substrate to give the desired product
in good yield (2r).
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a
a
Scheme 2. Scope of N-Benzyl Enaminoesters
Scheme 3. Scope of N-Substituted Enamines
a
Reaction conditions: 1 or 3 (0.3 mmol), TMSN3 (3 equiv), I2 (3
equiv), K2CO3 (3 equiv), and NaOAc (1 equiv) in DMF (6 mL) at 80
b
°C for 12 h. The reaction was carried out in CH3CN.
imidazole-4-carboxylic esters were obtained in 69% and 57%
yields (4f and g), respectively. Interestingly, the reaction of
enaminoester 3h containing a diphenyl phosphate group with
TMSN3 produced a 2-azidomethyl imidazole compound in
43% yield, which could be further employed to generate more
diversity through click reactions. The structure of 4h had been
further determined by crystallography analysis.
a
Reaction conditions: 1 (0.3 mmol), TMSN3 (3 equiv), I2 (3 equiv),
K2CO3 (3 equiv), and NaOAc (1 equiv) in DMF (6 mL) at 80 °C for
12 h.
To demonstrate the practical applicability of this method-
ology, a gram-scale reaction of 1a with TMSN3 was conducted
in an open flask, and the desired substituted imidazole-4-
carboxylic ester was isolated in 62% yield (Scheme 4a).
Furthermore, fused heteroaryl compound 2y (Scheme 4b),
which is a bioactive compound in the 1-H tautomeric form,13f
was effectively prepared under the standard reaction
conditions. Finally, hydrolysis of substituted imidazole-4-
carboxylic ester 2z, followed by condensation with 2-
aminothiazole, concisely produced the antiallergic agent 513b
(Scheme 4c).
In order to gain insights into the reaction mechanism, a
sequence of control experiments was performed in Scheme 5.
Reducing the reaction time to 5 min, besides the formation of
2a, hydrazine 6a was also isolated in 26% yield (Scheme 5a).
The structure of 6a was verified by single-crystal X-ray
diffraction analysis. To our surprise, without TMSN3, oxidation
of 6a also could give the target product 2a in 85% yield
(Scheme 5b). These observations indicated that 6a is a key
intermediate in the transformation. We further tested if 6a was
produced from diazo compounds, which could be easily
formed via ring-opening of the products from 1,3-dipolar
cycloaddition between enamines and azides (Scheme 5c).
However, the diazo 7 did not work under the reaction
Further assessment of the substrate scope for this reaction
was performed by treating more types of enamines with
TMSN3 (Scheme 3). To our delight, substrates with N-
substituted benzyl were participated well in this cyclization
process to give the desired products in 65−76% yields (2s−v).
Notably, the reaction of sterically hindered 2-methyl- or 2-
chloro-benzyl-substituted substrates proceeded well under the
optimized conditions, leading to the corresponding imidazole
products 2s or 2v in 76% and 72% yields, respectively.
Enaminoester 1w bearing a β-trifluoromethyl performed well
and afforded the substituted imidazole in 83%. Delightfully,
enaminone 1x was also tolerant, thereby furnishing the diaryl
ketone 2x in 58% yield. However, when −NO2- and −CN-
substituted enamines 1y and 1z were subjected to the current
conditions, no desired products were obtained. Extension of
the method to N-alkyl-substituted enaminoesters gave the
target imidazoles in moderate yields (4a−h). Notably, the
length of alkyl chains had little influence on the reaction.
Enaminoesters 3 possessing C2, C3, C5, and C8 N-alkyl chains
afforded the corresponding products in yields arranging from
40−51% (4a−d). Moreover, the substrates with functional
groups such as −OBn and −OPh on the alkyl substituents
were well tolerated, and the desired 2,5-disubstituted 1H-
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Scheme 4. Synthetic Applications
Scheme 5. Control Experiments
conditions, demonstrating that diazo compounds might not be
generated in the procedure. The reaction of 6a to 2a was
completely suppressed in the absence of iodine (Scheme 5d),
while 1.05 equiv of iodine could afford 83% yield of 2a
(Scheme 5e). The results indicated that iodine also played a
key role in this step. Compound 2a was produced in a good
yield from 6a in the absence of NaOAc, which revealed that
NaOAc might play an important role in the transformation of
1a to 6a (Scheme 5f). The addition of a radical scavenger, 2
equiv of TEMPO to the reaction system, gave 2a and 6a in
30% and 15% yields, respectively (Scheme 5g). Furthermore, a
radical clock experiment of enaminoester 3i was carried out,
and no ring-opening product was observed (Scheme 5h).
These results suggested that a radical pathway could be ruled
out in this transformation.
According to our experimental outcomes and previous
works,6,7 a proposed mechanism is presented in Scheme 6. The
initial 1,3-dipolar cycloaddition of enamine compounds 1 or 3
with TMSN3 generates 1,2,3-triazoline intermediate I.5b,5,17
Then, ring-opening of I gives α-azido enamine II.18 Further
base-induced intramolecular addition of N−N double bond
forms 2,3-dihydro-imidazol III, which is further oxidized by
iodine to give the hydrazine 6. Subsequent 6 is oxidized under
this I2/base system to couple with another molecule 6,
providing the 1,1′-azoimidazole IV.19 At last, hydrolysis of IV
produces the product 2 or 4.19 The role of iodine may be
versatile, besides the oxidant in the aromatization and
formation of III, as well as the useful catalyst in the steps of
1,3-dipolar cycloaddition and nucleophilic addition.
from TMSN3. The gram-scale reaction and derivatization of
the products may have potential applications in future organic
synthesis. Further investigations of the detailed reaction
mechanism are ongoing in our laboratory.
EXPERIMENTAL SECTION
General Information. All solvents and reagents were obtained
from commercial sources and used without further purification. H
■
1
NMR spectra obtained with tetramethylsilane (TMS, δ = 0 ppm) as
an internal standard in CDCl3 using an Agilent DD2 400-MR
spectrometer (400 MHz). Data were reported as follows: chemical
shift, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m =
multiplet, b = broad), coupling constant (J), and integration. 13C
NMR spectra were recorded on an Agilent DD2 400-MR
spectrometer (100 MHz). The chemical shifts were determined on
the δ-scale relative to CDCl3 (δ = 77.0 ppm). High-resolution mass
spectrometry was recorded on an AB SCIEX TOFTM 4600 MS
equipped with an electrospray ionization time-of-flight (ESI-TOF)
probe operating in the positive ion mode. The single-crystal X-ray
experiment was performed on an Agilent Xcalibur Eos Gemini
diffractometer equipped with graphite-monochromatized Cu Kα
radiation (λ = 1.5418 Å). Silica gel (200−300 mesh) was used for
column chromatographic separations and purifications. Petroleum
ether (PE) refers to the fraction boiling at 60−90 °C. Enamine
compounds 1 and 3 were known compounds and prepared by
CONCLUSION
■
In conclusion, we have developed an oxidative [4+1]
cyclization between enamines and TMSN3 under transition-
metal-free conditions, and a series of 2,5-disubstituted 1H-
imidazole-4-carboxylic derivatives bearing different substitu-
ents were synthesized efficiently. Moreover, the mechanistic
studies revealed that the reaction proceeds through an
unexpected sequential removal of the two nitrogen atoms
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128.7, 128.6, 126.0, 51.8, 21.4. HRMS (ESI-TOF) m/z: calcd for
C18H17N2O2 [M + H]+, 293.1285; found, 293.1291.
Scheme 6. Possible Reaction Mechanism
Methyl 2-Phenyl-5-(m-tolyl)-1H-imidazole-4-carboxylate (2c).
The product was obtained as a light yellow solid (60 mg, 68%)
1
(eluent: PE/EtOAc = 3:1). H NMR (400 MHz, CDCl3): δ 7.89−
7.92 (m, 2H), 7.50−7.53 (m, 2H), 7.35−7.37 (m, 3H), 7.19−7.23
(m, 1H), 7.10−7.13 (m, 1H), 3.76 (s, 3.H), 2.3 (s, 3H). 13C{1H}
NMR (100 MHz, CDCl3): δ 162.1, 147.5, 137.5, 131.4, 129.8, 129.7,
129.5, 128.8, 128.7, 127.7,126.5, 126.1, 51.7, 21.4. HRMS (ESI-TOF)
m/z: calcd for C18H17N2O2 [M + H]+, 293.1285; found ,293.1281.
Methyl 2-Phenyl-5-(o-tolyl)-1H-imidazole-4-carboxylate (2d).
The product was obtained as a white solid (33 mg, 38%) (eluent:
1
PE/EtOAc = 3:1). H NMR (400 MHz, CDCl3): δ 7.87−7.89 (m,
2H), 7.35−7.37 (m, 3H), 7.14−7.2 (m, 3H), 7.06−7.10 (m, 1H),
3.65 (m, 3H), 2.13 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ
162.3, 147.2, 137.4, 130.1, 129.9, 129.6, 128.9, 128.8, 126.0, 125.1,
51.6, 19.8. HRMS (ESI-TOF) m/z: calcd for C18H17N2O2 [M + H]+,
293.1285; found, 293.1297.
Methyl 4-(3,4-Dimethylphenyl)-2-phenyl-1H-imidazole-5-car-
boxylate (2e). The product was obtained as a light yellow solid (73
mg, 80%) (eluent: PE/EtOAc = 3:1). 1H NMR (400 MHz, CDCl3): δ
7.90−7.93 (m, 2H), 7.50−7.55 (m, 2H), 7.38−7.41 (m, 3H), 7.11−
7.13 (m, 1H), 3.81 (s, 3H), 2.25 (s, 6H). 13C{1H} NMR (100 MHz,
CDCl3): δ 161.7, 147.2, 137.4, 136.2, 130.2, 129.7, 129.2, 128.8,
126.7, 126.0, 51.7, 19.7, 19.6. HRMS (ESI-TOF) m/z: calcd for
C19H19N2O2 [M + H]+, 307.1441; found, 307.1452.
Methyl 4-(4-Methoxyphenyl)-2-phenyl-1H-imidazole-5-carboxy-
late (2f). The product was obtained as a light yellow solid (62 mg,
1
67%) (eluent: PE/EtOAc = 3:1). H NMR (400 MHz, CDCl3): δ
literatures,6b,11 and the spectra data were matched with the data
reported.
7.94−7.97 (m, 2H), 7.84−7.87 (m, 2H), 7.41−7.44 (m, 3H), 6.93−
6.95 (m, 2H), 3.86 (s, 3H), 3.83 (s, 3H). 13C{1H} NMR (100 MHz,
CDCl3): δ160.1, 147.1, 132.2, 132.1, 130.7, 130.0, 129.0, 128.6, 128.5,
126.0, 113.7, 113.5, 55.3, 51.8. HRMS (ESI-TOF) m/z: calcd for
C18H17N2O3 [M + H]+, 309.1233; found, 309.1240.
Experimental Procedures for the Synthesis of 2 or 4. A
sealed tube was charged with N-benzyl β-enamino esters 1 or 3 (0.3
mmol), DMF (6 mL), then K2CO3 (128 mg, 0.9 mmol, 3 equiv, 21.3
mg/mL), NaOAc (24.6 mg, 0.3 mmol, 1 equiv, 4.1 mg/mL), I2 (228
mg, 0.9 mmol, 3 equiv, 38 mg/L), and TMSN3 (104 mg, 0.9 mmol, 3
equiv, 17.3 mg/mL). The reaction mixture was stirred in an oil bath at
80 °C for 12 h. After the solution cooled to room temperature,
saturated brine (50 mL) was added to the mixture, and the solution
was extracted by EtOAc (40 mL × 3). The combined organic layer
was washed with water (50 mL × 2) and dried with anhydrous
Na2SO4. After removal of the solvent under reduced pressure, the
residue was separated by flash column chromatography to afford the
pure product 2 or 4.
Methyl 4-(3-Methoxyphenyl)-2-phenyl-1H-imidazole-5-carboxy-
late (2g). The product was obtained as a light yellow solid (53 mg,
1
57%) (eluent: PE/EtOAc = 3:1). H NMR (400 MHz, CDCl3): δ
7.93−7.96 (m, 2H), 7.41−7.47 (m, 5H), 7.28−7.32 (m, 1H), 6.90−
6.93 (m, 1H), 3.84 (s, 3H), 3.83 (s, 3H). 13C{1H} NMR (100 MHz,
CDCl3): δ 161.3, 159.2, 147.4, 133.3, 130.0, 129.0, 128.9, 128.5,
126.0, 121.7, 114.9, 114.5, 55.3, 51.9. HRMS (ESI-TOF): m/z calcd
for C18H17N2O3 [M + H]+, 309.1233; found, 309.1241.
Methyl 4-(3,4-Dimethoxyphenyl)-2-phenyl-1H-imidazole-5-car-
boxylate (2h). The product was obtained as a light yellow solid
(82 mg, 81%) (eluent: PE/EtOAc = 3:1). 1H NMR (400 MHz,
CDCl3): δ 7.94−7.97 (m, 2H), 7.51−7.57 (m, 2H),7.40−7.45 (m,
3H), 6.88−6.90 (m, 1H), 3.91 (s, 3H), 3.89 (s, 3H), 3.85 (s, 3H).
13C{1H} NMR (100 MHz, CDCl3): δ 161.3, 149.5, 148.3, 147.2,
Gram-Scale Synthesis of 2a. A 100 mL round-bottom flask was
charged with N-benzyl β-enamino esters 1 (1.34 g, 5 mmol, 26.8 mg/
mL), DMF (50 mL), then K2CO3 (2.07 g, 15 mmol, 3 equiv, 41.5
mg/mL), NaOAc (410 mg, 5 mmol, 1 equiv, 8.2 mg/mL), I2 (3.81 g,
15 mmol, 3 equiv, 76.1 mg/mL), and TMSN3 (1.73 g, 15 mmol, 3
equiv, 34.5 mg/mL). The reaction mixture was stirred in an oil bath at
80 °C for 12 h. After the solution cooled to room temperature,
saturated brine (200 mL) was added to the mixture, and the solution
was extracted by EtOAc (100 mL × 3). The combined organic layer
was washed with water (100 mL × 2) and dried with anhydrous
Na2SO4. After removal of the solvent under reduced pressure, the
residue was separated by flash column chromatography to afford the
pure product 2a (862 mg, 62%) (eluent: PE/EtOAc = 3:1).
Methyl 2,5-Diphenyl-1H-imidazole-4-carboxylate (2a).14a The
product was obtained as a light yellow solid (71 mg, 85%) (eluent:
130.0, 128.9, 128.6, 126.0, 122.1, 112.6, 110.6, 55.9, 55.8, 51.8.
HRMS (ESI-TOF): m/z calcd for C19H19N2O4 [M + H]+, 339.1339;
found, 339.1356.
Methyl 4-(4-Fluorophenyl)-2-phenyl-1H-imidazole-5-carboxy-
late (2i). The product was obtained as a white solid (54 mg, 61%)
1
(eluent: PE/EtOAc = 3:1). H NMR (400 MHz, CDCl3): δ 7.92−
7.96 (m, 4H), 7.43−7.49 (m, 3H), 7.08−7.13 (m, 2H), 7.87 (s, 3H),
3.87 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 163.1 (d, JC−F
=
247 Hz), 160.8, 147.5, 131.2 (d, JC−F = 8 Hz), 130.1, 129.0, 128.4,
126.0, 114.9 (d, JC−F = 21 Hz), 51.9. HRMS (ESI-TOF): m/z calcd
for C17H14FN2O2 [M + H]+, 297.1033; found, 297.1052.
1
PE/EtOAc = 3:1). H NMR (400 MHz, CDCl3): δ 7.92−7.95 (m,
Methyl 4-(4-Chlorophenyl)-2-phenyl-1H-imidazole-5-carboxy-
2H), 7.84−7.86 (m, 2H), 7.36−7.45 (m, 6H), 3.84 (s, 3H). 13C{1H}
NMR (100 MHz, CDCl3): δ 161.5, 147.5, 129.9, 129.2, 128.9, 128.8,
128.7, 128.0, 126.0, 51.8. HRMS (ESI-TOF) m/z: calcd for
C17H15N2O2 [M + H]+, 279.1128; found, 279.1131.
late (2j). The product was obtained as a light yellow solid (70 mg,
1
75%) (eluent: PE/EtOAc = 3:1). H NMR (400 MHz, CDCl3): δ
7.93−7.95 (m, 4H), 7.43−7.47 (m, 3H), 7.37−7.40 (m, 2H), 3.87 (s,
3H). 13C{1H} NMR (100 MHz, CDCl3): δ 134.6, 130.6, 130.1, 129.0,
128.6, 128.2, 125.9, 52.1. HRMS (ESI-TOF): m/z calcd for
C17H14ClN2O2 [M + H]+, 313.0738; found, 313.0747.
Methyl 5-(3-Chlorophenyl)-2-phenyl-1H-imidazole-4-carboxy-
late (2k). The product was obtained as a light yellow solid (64 mg,
68%) (eluent: PE/EtOAc = 3:1).1H NMR (400 MHz, CDCl3): δ
10.20 (b, 1H), 7.94−8.00 (m, 3H), 7.86−7.90 (m, 1H), 7.44−7.48
Methyl 2-Phenyl-5-(p-tolyl)-1H-imidazole-4-carboxylate (2b).
The product was obtained as a light yellow solid (61 mg, 70%)
1
(eluent: PE/EtOAc = 3:1). H NMR (400 MHz, CDCl3): δ 7.92−
7.95 (m, 2H), 7.74−7.76 (m, 2H), 7.40−7.45 (m, 3H), 7.20−7.22
(m, 2H), 3.84 (s, 3H), 2.37 (s, 3H). 13C{1H} NMR (100 MHz,
CDCl3): δ 161.5, 147.2, 138.8, 130.2, 129.9, 129.2, 129.1, 128.9,
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(m, 3H), 7.33−7.35 (m, 2H), 3.88 (s, 3H). 13C{1H} NMR (100
MHz, CDCl3): δ 160.5, 148.0, 146.9, 134.9, 133.8, 130.2, 129.3,
129.2, 129.1, 128.5, 127.4, 126.0, 118.5, 52.1. HRMS (ESI-TOF): m/
z calcd for C17H14ClN2O2 [M + H]+, 313.0738; found, 313.0742.
Methyl 5-(4-Bromophenyl)-2-phenyl-1H-imidazole-4-carboxy-
late (2l). The product was obtained as a light yellow solid (74 mg,
4H), 7.32−7.38 (m, 3H), 7.18−7.20 (m, 2H), 3.78 (s, 3H), 2.36 (s,
3H). 13C{1H} NMR (100 MHz, CDCl3): δ 161.8, 147.8, 140.0, 131.9,
129.5, 129.2, 128.6, 127.9, 126.1, 126.0, 51.7, 21.4. HRMS (ESI-
TOF): m/z calcd for C18H17N2O2 [M + H]+, 293.1285; found,
293.1287.
Methyl 2-(4-Methoxyphenyl)-5-phenyl-1H-imidazole-4-carboxy-
1
69%) (eluent: PE/EtOAc = 3:1). H NMR (400 MHz, CDCl3): δ
late (2u). The product was obtained as a yellow solid (60 mg, 65%)
1
7.94−7.97 (m, 2H), 7.84−7.86 (m, 2H), 7.54−7.56 (m, 2H), 7.45−
7.49 (m, 3H), 3.88 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ
160.6, 147.6, 131.2, 130.9, 130.4, 129.1, 127.9, 126.1, 123.2, 52.1.
HRMS (ESI-TOF): m/z calcd for C17H13NaBrN2O2 [M + Na]+,
379.0052; found, 379.0059.
(eluent: PE/EtOAc = 3:1). H NMR (400 MHz, CDCl3): δ 7.83−
7.88 (m, 4H), 7.35−7.42 (m, 3H), 6.92−6.95 (m, 2H), 3.83 (s, 3H),
3.82 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 161.5, 161.0,
147.6, 132.3, 129.2, 128.6, 128.3, 127.9, 127.5, 127.0, 121.5, 114.3,
55.4, 51.7. HRMS (ESI-TOF): m/z calcd for C18H17N2O3 [M + H]+,
309.1234; found, 309.1228.
Methyl 2-Phenyl-4-(4-(trifluoromethyl)phenyl)-1H-imidazole-5-
carboxylate (2m). The product was obtained as a white solid 77
mg, 74%) (eluent: PE/EtOAc = 3:1). 1H NMR (400 MHz, CDCl3): δ
8.08−8.10 (m, 2H), 7.95−7.97 (m, 2H), 7.66−7.69 (m, 2H), 7.45−
7.49 (m, 3H), 3.88 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ
160.6, 147.9, 130.5, 130.3, 130.2, 129.6, 129.1, 128.4, 126.2, 126.0,
125.5, 124.9 (q, JC−F = 3.81 Hz), 122.8, 52.1. HRMS (ESI-TOF): m/z
calcd for C18H14F3N2O2 [M + H]+, 347.1001; found, 347.1004.
Methyl 2-Phenyl-4-(thiophen-2-yl)-1H-imidazole-5-carboxylate
(2n). The product was obtained as a light yellow solid (57 mg,
Methyl 2-(2-Chlorophenyl)-5-phenyl-1H-imidazole-4-carboxy-
late (2v).13a The product was obtained as a yellow solid (63 mg,
1
72%) (eluent: PE/EtOAc = 3:1). H NMR (400 MHz, CDCl3): δ
7.70 (dd, J = 8.1, 1.6 Hz, 2H), 7.54 (dd, J = 7.4, 1.9 Hz, 1H), 7.49
(dd, J = 8.2, 1.2 Hz, 1H), 7.35−7.45 (m, 6H), 3.81 (s, 3H). 13C{1H}
NMR (100 MHz, CDCl3): δ 161.9, 147.9, 146.6, 134.5, 133.9, 132.3,
131.2, 129.5, 129.4, 129.2, 128.9, 128.3, 127.7, 126.9, 117.7, 51.6.
HRMS (ESI-TOF): m/z calcd for C17H14ClN2O2 [M + H]+,
313.0744; found, 313.0739.
1
67%) (eluent: PE/EtOAc = 3:1). H NMR (400 MHz, CDCl3): δ
Ethyl 2-Phenyl-5-(trifluoromethyl)-1H-imidazole-4-carboxylate
(2w).6b The product was obtained as a white solid (71 mg, 83%)
10.47 (b. 1H), 7.95−8.05 (m, 3H), 7.36−7.40 (m, 4H), 7.06−7.09
(m, 1H), 3.90 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 160.6,
148.1, 142.5, 136.3, 130.1, 128.9, 128.5, 128.3, 127.5, 127.1, 126.2,
116.8, 52.0. HRMS (ESI-TOF): m/z calcd for C15H13N2O2S [M +
H]+, 285.0692; found, 285.0712.
1
(eluent: PE/EtOAc = 3:1). H NMR (400 MHz, CDCl3): δ 7.94−
7.97 (m, 2H), 7.44−7.47 (m, 3H), 4.41 (q, J = 7.1 Hz, 2H), 1.39 (t, J
= 7.1 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 159.4, 148.1,
136.1 (q, JC−F = 39.3 Hz), 130.5, 128.9, 128.0, 126.4, 121.7 (q, JC−F
=
Methyl 2-Phenyl-5-(thiophen-3-yl)-1H-imidazole-4-carboxylate
2.3 Hz), 120.7 (q, JC−F = 268 Hz), 62.3, 13.8. HRMS (ESI-TOF): m/
z calcd for C13H12F3N2O2 [M + H]+, 285.0845; found, 285.0847.
(2,4-Diphenyl-1H-imidazol-5-yl)(phenyl)methanone (2x).16b The
product was obtained as a light yellow solid (56 mg, 58%) (eluent:
(2o). The product was obtained as a light yellow solid (63 mg,
1
74%) (eluent: PE/EtOAc = 3:1). H NMR (400 MHz, CDCl3): δ
8.17−8.18 (m, 1H), 7.92−7.94 (m, 2H), 7.18−7.80 (m, 1 H), 7.41−
7.45 (m, 3H), 7.32−7.34 (m, 1H), 3.90 (s, 3H). 13C{1H} NMR (100
MHz, CDCl3): δ 161.0, 147.3, 130.0, 128.9, 128.8, 128.6, 128.4,
127.9, 126.0, 125.9, 124.8, 51.9. HRMS (ESI-TOF): m/z calcd for
C15H13N2O2S [M + H]+, 285.0692; found, 285.0707.
1
PE/EtOAc = 3:1). H NMR (400 MHz, CDCl3): δ 12.00 (b, 1H),
8.19−8.21 (m, 2H), 7.57−7.60 (m, 2H), 7.29−7.42 (m, 3H), 7.12−
8.15 (m, 3H), 7.05−7.09 (m, 5H). 13C{1H} NMR (100 MHz,
CDCl3): δ 187.7, 150.8, 149.9, 137.2, 133.7, 132.3, 130.1,129.9, 129.6,
128.8, 128.0, 127.9, 127.8, 127.6, 126.7. HRMS (ESI-TOF): m/z
calcd for C22H17N2O [M + H]+, 325.1341; found, 325.1351.
2-Phenylchromeno[3,4-d]imidazol-4(1H)-one (2y).13f The prod-
uct was obtained as a light yellow solid (67 mg, 85% yield) (eluent:
PE/EtOAc = 3:1). 1H NMR (400 MHz, DMSO-d6): δ 13.81 (b, 1H),
8.07−8.17 (m, 3H), 7.38−7.55 (m, 6H). 13C{1H} NMR (100 MHz,
DMSO-d6): δ 169.5, 152.3, 140.0, 130.7, 130.0, 129.4, 128.7, 127.7,
127.1, 126.9, 125.0, 122.7, 117.4. HRMS (ESI-TOF): m/z calcd for
C16H10N2O2 [M + H]+, 263.0815; found, 263.0811.
Methyl 4-([1,1′-Biphenyl]-4-yl)-2-phenyl-1H-imidazole-5-carbox-
ylate (2p). The product was obtained as a light yellow solid (72 mg,
1
68%) (eluent: PE/EtOAc = 3:1). H NMR (400 MHz, CDCl3): δ
7.97−8.01 (m, 4H), 7.61−7.67 (m, 4H), 7.42−7.47 (m, 5H), 7.33−
7.37 (m, 1H), 3.89 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ
161.2, 147.4, 141.5, 140.7, 130.7, 130.2, 129.7, 129.0, 128.9, 128.8,
128.3, 127.5, 127.3, 127.1, 126.7, 126.1, 52.0. HRMS (ESI-TOF): m/
z calcd for C23H19N2O2 [M + H]+, 355.1441; found, 355.1454.
Methyl 4-(Naphthalen-1-yl)-2-phenyl-1H-imidazole-5-carboxy-
late (2q). The product was obtained as a light yellow solid (47 mg,
1
Methyl 2-(Naphthalen-1-yl)-5-(p-tolyl)-1H-imidazole-4-carboxy-
48%) (eluent: PE/EtOAc = 3:1). H NMR (400 MHz, CDCl3): δ
late (2z).13b The product was obtained as a yellow solid (55 mg,
7.91-7.93 (m, 2H), 7.85−7.89 (m, 2H), 7.77 (m, 1H), 7.52−7.53 (m,
1H), 7.44−7.49 (m, 2H), 7.38−7.43 (m, 4H), 3.61 (s, 3H). 13C{1H}
NMR (100 MHz, CDCl3): δ 133.5, 132.0, 129.8, 129.3, 129.0, 128.8,
128.5, 128.3, 126.3, 125.9, 125.6, 124.9, 51.7. HRMS (ESI-TOF): m/
z calcd for C21H17N2O2 [M + H]+, 329.1284; found, 329.1293.
Ethyl 2,4-diphenyl-1H-imidazole-5-carboxylate (2r).6b The prod-
uct was obtained as a white solid (70 mg, 80%) (eluent: PE/EtOAc =
3:1). 1H NMR (400 MHz, CDCl3): δ 7.94−7.96 (m, 2H), 7.83−7.85
(m, 2H), 7.32−7.44 (m, 6H), 4.27−4.34 (m, 2H), 1.24−1.30 (m,
3H). 13C{1H} NMR (100 MHz, CDCl3): δ 161.1, 147.6, 132.3, 129.8,
129.4, 128.9, 128.6, 127.8, 126.1, 61.0, 14.2. HRMS (ESI-TOF): m/z
calcd for C18H17N2O2 [M + H]+, 293.1284; found, 293.1289.
Methyl 5-Phenyl-2-(o-tolyl)-1H-imidazole-4-carboxylate (2s).
The product was obtained as yellow oil (67 mg, 76%) (eluent: PE/
1
54%) (eluent: PE/EtOAc = 3:1). H NMR (400 MHz, CDCl3): δ
8.55−8.57 (m, 1H), 7.83−7.93 (m, 4H), 7.68−7.70 (m, 1H), 7.51−
7.55 (m, 2H), 7.45−7.49 (m, 1H), −7.26 (m, 1H), 7.23−7.24 (m,
1H), 3.82 (s, 3H), 2.39 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3):
δ 161.5, 147.1, 138.8, 133.8, 130.9, 130.5, 129.2, 128.8, 128.5, 127.4,
126.5, 126.4, 125.5, 124.9, 51.8, 21.4. HRMS (ESI-TOF): m/z calcd
for C22H18N2O2 [M + H]+, 343.1441; found, 343.1441.
Methyl 2-methyl-5-phenyl-1H-imidazole-4-carboxylate (4a).16c
The product was obtained as a light yellow oil (33 mg, 51%) (eluent:
1
PE/EtOAc = 3:1). H NMR (400 MHz, CDCl3): δ 10.27 (b, 1H),
7.67 (dd, J = 7.6, 2.1 Hz, 2H)), 7.29−7.33 (m, 3H), 3.74 (s, 3H), 2.25
(s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 162.2, 146.3, 142.8,
131.2, 129.1, 128.6, 128.0, 121.3, 51.6, 13.6. HRMS (ESI-TOF): m/z
calcd for C12H13N2O2 [M + H]+, 217.0971; found, 217.0967.
Methyl 2-Ethyl-5-phenyl-1H-imidazole-4-carboxylate (4b). The
product was obtained as a light yellow oil (35 mg, 51%) (eluent: PE/
EtOAc = 3:1). 1H NMR (400 MHz, CDCl3): δ 7.73 (dd, J = 8.1, 1.6
Hz, 2H), 7.31−7.37 (m, 3H), 3.78 (s, 3H), 2.71 (q, J = 7.6 Hz, 1H),
1.27 (t, J = 7.7 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 161.8,
151.4, 131.9, 129.1, 128.5, 127.5, 120.2, 51.6, 21.7, 12.3. HRMS (ESI-
TOF): m/z calcd for C13H15N2O2 [M + H]+, 231.1128; found,
231.1127.
1
EtOAc = 3:1). H NMR (400 MHz, CDCl3): δ 7.83−7.86 (m, 2H),
7.45 (d, J = 7.6 Hz, 1H), 7.29−7.40 (m, 5H), 7.15−7.19 (m, 1H),
3.78 (s, 3H), 2.47 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ
161.5, 148.0, 146.5, 138.2, 136.9, 134.0, 131.1, 129.6, 129.2, 129.1,
128.6, 127.9, 127.7, 125.9, 51.7, 20.7. HRMS (ESI-TOF): m/z calcd
for C18H17N2O2 [M + H]+, 293.1290; found, 293.1287.
Methyl 5-Phenyl-2-(m-tolyl)-1H-imidazole-4-carboxylate (2t).
The product was obtained as a yellow solid (61 mg, 70%) (eluent:
1
PE/EtOAc = 3:1). H NMR (400 MHz, CDCl3): δ 7.67−7.81 (m,
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Methyl 2-Butyl-5-phenyl-1H-imidazole-4-carboxylate (4c).16c
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c01145.
■
The product was obtained as a light yellow oil (35 mg, 45%) (eluent:
sı
1
PE/EtOAc = 3:1). H NMR (400 MHz, CDCl3): δ 9.72 (b, 1H),
7.68−7.70 (m, 2H), 7.29−7.34 (m, 3H), 3.75 (s, 3H), 2.58 (t, J = 7.9
Hz, 2H), 1.53−1.61 (m, 2H), 1.19−1.29 (m, 2H), 0.81 (t, J = 7.47
Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 162.1, 150.6, 143.3,
131.6, 129.1, 128.5, 127.9, 120.8, 51.6, 30.4, 28.0, 22.3, 13.7. HRMS
(ESI-TOF): m/z calcd for C15H19N2O2 [M + H]+, 259.1441; found,
259.1458.
Copies of NMR spectra and X-ray structures (PDF)
Accession Codes
CCDC 2054878−2054879 and 2054889 contain the supple-
mentary crystallographic data for this paper. These data can be
obtained free of charge via www.ccdc.cam.ac.uk/data_request/
cif, or by emailing data_request@ccdc.cam.ac.uk, or by
contacting The Cambridge Crystallographic Data Centre, 12
Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
Methyl 2-Heptyl-5-phenyl-1H-imidazole-4-carboxylate (4d). The
product was obtained as a light yellow oil (36 mg, 40%) (eluent: PE/
1
EtOAc = 3:1). H NMR (400 MHz, CDCl3): δ 7.74−7.76 (m, 2H),
7.33−7.39 (m, 3H), 3.80 (s, 3H), 2.67 (t, J = 7.9 Hz, 2H), 1.64−1.71
(m, 2H), 1.21−1.28 (m, 8H), 0.84 (t, J = 6.7 Hz, 3H). 13C{1H} NMR
(100 MHz, CDCl3): δ 161.7, 150.6, 132.9, 131.8, 130.0, 129.1, 128.3,
128.0, 51.7, 31.6, 29.3, 28.9, 28.5, 28.3, 22.6, 14.1. HRMS (ESI-
TOF): m/z calcd for C18H25N2O2 [M + H]+, 301.1910; found,
301.1897.
AUTHOR INFORMATION
Corresponding Author
■
Peng Gao − Shaanxi Key Laboratory of Phytochemistry,
College of Chemistry and Chemical Engineering, Baoji
University of Arts and Sciences, Baoji, Shaanxi 721013, P. R.
China; Key Laboratory of Synthetic and Natural Functional
Molecule Chemistry of Ministry of Education, Department of
Chemistry & Materials Science, Northwest University, Xi’an
710127, P. R. China; orcid.org/0000-0003-1292-0691;
Email: gaopeng_hx@bjwlxy.edu.cn
Methyl 2-Benzyl-5-phenyl-1H-imidazole-4-carboxylate (4e). The
product was obtained as a light yellow oil (44 mg, 50%) (eluent: PE/
1
EtOAc = 3:1). H NMR (400 MHz, CDCl3): δ 7.70−7.72 (m, 2H),
7.31−7.37 (m, 3H), 7.22−7.29 (m, 3H), 7.15−7.18 (m, 2H), 4.01 (s,
2H), 3.74 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 161.8,
148.6, 136.1, 131.5, 129.3, 129.1, 128.9, 128.8, 128.6, 128.0, 127.9,
127.2, 51.6, 34.8. HRMS (ESI-TOF): m/z calcd for C18H17N2O2 [M
+ H]+, 293.1284; found, 293.1279.
Authors
Methyl 2-((Benzyloxy)methyl)-5-phenyl-1H-imidazole-4-carbox-
ylate (4f). The product was obtained as a light yellow oil (67 mg,
Huaijuan Chen − Shaanxi Key Laboratory of Phytochemistry,
College of Chemistry and Chemical Engineering, Baoji
University of Arts and Sciences, Baoji, Shaanxi 721013, P. R.
China
Zi-Jing Bai − Shaanxi Key Laboratory of Phytochemistry,
College of Chemistry and Chemical Engineering, Baoji
University of Arts and Sciences, Baoji, Shaanxi 721013, P. R.
China
Sheng Zhang − Shaanxi Key Laboratory of Phytochemistry,
College of Chemistry and Chemical Engineering, Baoji
University of Arts and Sciences, Baoji, Shaanxi 721013, P. R.
China; orcid.org/0000-0001-9370-0548
Mi-Na Zhao − Shaanxi Key Laboratory of Phytochemistry,
College of Chemistry and Chemical Engineering, Baoji
University of Arts and Sciences, Baoji, Shaanxi 721013, P. R.
China; orcid.org/0000-0001-7937-9284
Desuo Yang − Shaanxi Key Laboratory of Phytochemistry,
College of Chemistry and Chemical Engineering, Baoji
University of Arts and Sciences, Baoji, Shaanxi 721013, P. R.
China; orcid.org/0000-0002-7190-3122
Yingchun Li − Shaanxi Key Laboratory of Phytochemistry,
College of Chemistry and Chemical Engineering, Baoji
University of Arts and Sciences, Baoji, Shaanxi 721013, P. R.
China
1
69%) (eluent: PE/EtOAc = 3:1). H NMR (400 MHz, CDCl3): δ
7.73−7.76 (m, 2H), 7.29−7.40 (m, 8H), 4.63 (s, 2H), 4.57 (s, 2H),
3.81 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 161.6, 146.5,
136.9, 129.4, 129.1, 128.7, 128.6, 128.2, 128.1, 127.7, 73.4, 65.3, 51.7.
HRMS (ESI-TOF): m/z calcd for C19H19N2O3 [M + H]+, 323.1390;
found, 323.1379.
Methyl 2-(Phenoxymethyl)-5-phenyl-1H-imidazole-4-carboxy-
late (4g). The product was obtained as a light yellow solid (53 mg,
1
57%) (eluent: PE/EtOAc = 3:1). H NMR (400 MHz, CDCl3): δ
7.80 (dd, J = 8.1, 1.6 Hz, 2H), 7.38−7.44 (m, 3H), 7.28−7.32 (m,
2H), 6.95−7.03 (m, 3H), 5.22 (s, 2H), 3.84 (s, 3H). 13C{1H} NMR
(100 MHz, CDCl3): δ 157.5, 129.8, 129.1, 129.0, 128.2, 122.1, 114.6,
63.4, 51.9. HRMS (ESI-TOF): m/z calcd for C18H17N2O3 [M + H]+,
309.1233; found, 309.1227.
Methyl 2-(Azidomethyl)-5-phenyl-1H-imidazole-4-carboxylate
(4h). The product was obtained as a light yellow oil (33 mg, 43%)
(eluent: PE/EtOAc = 3:1). 1H NMR (400 MHz, CDCl3): δ 7.71 (dd,
J = 7.5, 2.2 Hz, 2H), 7.34−7.39 (m, 3H), 4.41 (s, 2H), 3.79 (s, 3H).
13C{1H} NMR (100 MHz, CDCl3): δ 161.8, 143.8, 130.9, 129.1,
128.9, 128.8, 128.1, 120.0, 51.8, 47.5. HRMS (ESI-TOF): m/z calcd
for C12H12N5O2 [M + H]+, 258.0985; found, 258.0973.
Methyl 2-Cyclopropyl-5-phenyl-1H-imidazole-4-carboxylate (4i).
The product was obtained as a light yellow oil (34 mg, 47%) (eluent:
PE/EtOAc = 3:1). 1H NMR (400 MHz, CDCl3): δ 7.73 (dd, J = 8.1,
1.6 Hz, 2H), 7.32−7.37 (m, 3H), 3.78 (s, 3H), 1.90−1.97 (m, 1H),
1.02−1.07 (m, 2H), 0.97−1.01 (m, 2H). 13C{1H} NMR (100 MHz,
CDCl3): δ 161.4, 151.8, 132.0, 129.2, 128.5, 127.9, 119.2, 51.6, 29.7,
9.0, 8.2. HRMS (ESI-TOF): m/z calcd for C14H14N2O2 [M + H]+,
243.1128; found, 243.1122.
Methyl 1-Amino-2,4-diphenyl-1H-imidazole-5-carboxylate (6a).
The product was obtained as a light yellow solid (23 mg, 26%)
(eluent: PE/EtOAc = 3:1). 1H NMR (400 MHz, CDCl3): δ 8.14 (dd,
J = 7.5, 2.2 Hz, 2H), 7.67 (dd, J = 8.0, 1.6 Hz, 2H), 7.35−7.45 (m,
6H), 5.64 (s, 2H), 3.77 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3):
δ 161.7, 148.7, 146.9, 129.7, 129.5, 129.3, 128.3, 128.2, 127.7, 118.1,
65.5, 60.4, 51.5. HRMS (ESI-TOF): m/z calcd for C17H15N3O2 [M +
H]+, 294.1237; found, 294.1241.
Jiangwei Zhang − State Key Laboratory of Catalysis, Dalian
Institute of Chemical Physics, Chinese Academy of Sciences
(CAS), Dalian 116023, China; orcid.org/0000-0002-
1221-3033
Xiaomei Wang − Shaanxi Key Laboratory of Phytochemistry,
College of Chemistry and Chemical Engineering, Baoji
University of Arts and Sciences, Baoji, Shaanxi 721013, P. R.
China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c01145
Notes
The authors declare no competing financial interest.
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(7) (a) Foley, C.; Shaw, A.; Hulme, C. Aza-Riley Oxidation of Ugi-
Azide and Ugi-3CR Products toward Vicinal Tricarbonyl Amides:
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ACKNOWLEDGMENTS
■
Financial support from the China Postdoctoral Science
Foundation (2019T120936), Natural Science Foundation of
Shaanxi Province (2019JQ-274), Undergraduate Innovation
and Entrepreneurship Training Program of China
(S202010721015), Scientific Research Foundation of Shaanxi
Provincial Key Laboratory (19JS004), and Baoji University of
Arts and Sciences (2020XJ015 and YJSCX20YB20) are
gratefully acknowledged. We also thank Prof. Zheng-Hui
Guan (Northwest University) for collaboration.
(8) Ghosh, A. K.; Brindisi, M.; Sarkar, A. The Curtius Rearrange-
ment: Applications in Modern Drug Discovery and Medicinal
Chemistry. ChemMedChem 2018, 13, 2351−2373.
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Coupler for Magnetic Coordination Polymers. Coord. Chem. Rev.
2019, 382, 1−31.
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Lin, Z.; Namikawa, K.; Elliott, S. L.; Köster, R. W.; Parak, W. J.;
Meggers, E. Catalytic Azide Reduction in Biological Environments.
ChemBioChem 2012, 13, 1116−1120.
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