Annulation of Conjugated Azine-Imine with a Sulfoxonium Ylide in a Noncarbenoid Route to Synthesize Multisubstituted Imidazole-Fused Heterocycles

Article abstract of DOI:10.1021/acs.joc.1c00052

A new [4+1]-annulation of in situ generated heterocyclic azine-aldimines with β-keto sulfoxonium ylides has been developed. The reaction constructs N-fused imidazole rings. In the reaction, the ylides play a dual-functional role of a nucleophilic 1,1-dipo

Full text of DOI:10.1021/acs.joc.1c00052

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Annulation of Conjugated Azine-Imine with a Sulfoxonium Ylide in a
Noncarbenoid Route to Synthesize Multisubstituted Imidazole-
Fused Heterocycles
Sankar K. Guchhait,* Meenu Saini, Viren J. Khivsara, and Santosh K. Giri
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ABSTRACT: A new [4+1]-annulation of in situ generated
heterocyclic azine-aldimines with β-keto sulfoxonium ylides has
been developed. The reaction constructs N-fused imidazole rings.
In the reaction, the ylides play a dual-functional role of a
nucleophilic 1,1-dipolar one-carbon synthon and a source of an
internal oxidant, dimethyl sulfoxide, that promotes in situ
dehydrogenation to product scaffolds. The method enables access to imidazo-pyridine, pyrazine, and pyrimidine heteroaromatics.
Scheme 1. Sulfoxonium Ylides’ Carbenoid and
Noncarbenoid Chemistry and Present Work
ulfur-based ylides are among the important functional
Ssubstrates used in various synthetic organic chemistry
transformations.1 Their functions as carbene equivalents in the
cyclization reactions with diverse unsaturated electrophilic
functional motifs have been widely documented, which afford
the synthesis of a range of heterocyclic and carbocyclic
compounds.2 Sulfoxonium ylides are stable, crystalline solids,
operationally safe, and, thus, employed as popular carbene
surrogates. They are used in X−H (X = C, N, O, S) and other
bond insertion reactions.3 Transition-metal-catalyzed sp2 C−H
activation/insertion−annulation reactions with β-ketosulfoxo-
nium ylides as carbene equivalents are especially appealing and
have been widely discovered (Scheme 1A).4 The β-
ketosulfoxonium ylide functions as a traceless bifunctional
directing motif in arene C−H functionalization and post-
annulation reactions.4h,5 All of these transformations involve
transition-metal-carbenoid chemistry. Recently, a divergent
[2+1+1+1]-annulation of ButONO with an aroylsulfoxonium
ylide as a carbene precursor has been developed, which
provides furoxans and isoxazoles.6 The study of a sulfoxonium
ylide as a 1,1′-dipolar one-carbon synthon, avoiding transition-
metal-carbenoid chemistry, is rare in annulation reactions
(Scheme 1B)7 and has not been identified until now for the
construction of fused heteroaromatics. In the aspect of a
unique feature of ylides, we previously explored nitrile-
stabilized ammonium ylide as a masked C−CN synthon
(Scheme 1C).8 In the study of the β-ketosulfoxonium ylide as a
nucleophilic 1,1′-dipolar species toward the preparation of
therapeutically important N-fused imidazoles,9 we realized a
[4+1]-annulation reaction of the ylides with a suitable 1,3-
conjugated system, heterocyclic amidine-derived imine
(Scheme 1D).
Received: January 8, 2021
Published: March 24, 2021
Imidazopyridines are important heterocyclic scaffolds
because of their versatile applications in the field of
medicinal,10 material,11 and organometallic chemistry.12 The
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scaffold is present in several drugs including zolpidem,13
olprinone,14 minodronic acid15 and zolimidine,16 and a clinical
candidate Q203.17 3-Aroylimidazo[1,2-a]pyridines have been
ascribed to a broad spectrum of biological activities, such as an
anticancer and calcium antagonist.18 We also have explored
synthetic methods and biological properties of various N-fused
imidazoles, especially imidazo[1,2-a]pyridines/pyrazines.19
Toward the synthesis of 2-aryl-3-aroylimidazo[1,2-a]pyridines,
the frequently considered approach is the reaction of
aminopyridine with chalcone.20,21 Other methods include
C−H functionalization of N-aryl enamine,22 CBr4-mediated
oxidative C−N bond formation of 2-aminopyridines with 1,3-
dicarbonyls,23 and a reaction of 2-aminopyridine and benzyl
bromide with a terminal alkyne.24 In light of this synthetic
precedence, our envisaged ylide-based [4+1]-annulation
approach would afford a new convenient diversity-feasible
synthesis of 2-ary-3-aroyl-imidazo[1,2-a]pyridines/pyrazines.
In the preliminary investigation, 4-chlorophenacylsulfoxo-
nium ylide 1 was chosen as a model ylide substrate (Table 1).
the desired 2-aryl-3-aroyl-imidazo[1,2-a]pyridine in a 42%
isolated yield (entry 1). p-TSA as an additive along with
Cu(OTf)2 improved the yield (entry 2). We observed that
imine formation could not be made complete in numerous
conditions. Variation in equivalents of aldehyde and amine
indicated that 1.3 equiv of each of them were optimal to
enhance the yield (entries 3−5). The reaction in the absence
of Cu(OTf)2 reduced the yield significantly, indicating the
importance of a Lewis acid. A variety of Lewis acids (entries
7−21) were screened. A few Lewis acids (Cu, Yb, Sc-based)
were found to be effective, and CuCl2 was found to be the best
(entry 17).
Imine formation is reversible and sensitive to pH. In
addition, the use of p-TSA in the reaction increased the yield.
These indicated a possible effect of the pKa of a Brønsted acid
in the reaction. Accordingly, acids with different pKa values
replacing p-TSA were evaluated (Table 2A). Acids with pKa
a
Table 2A. Evaluation of Brønsted Acids
b
entry
additive (10 mol %)
pKa
−13
−7
−2
−1.76
0.0
yield (%)
a
Table 1. Evaluation of Lewis Acids
1
2
3
4
5
6
7
8
9
TfOH
HCl
MsOH
p-TSA
CF3COOH
Picric acid
CH3COOH
PhB(OH)2
H3BO3
50
55
71
76
78
69
56
48
31
0.3
4.75
8.83
9.23
b
entry
equiv of 1 and 2
Lewis acid (mol %)
yield (%)
c
1
1
1
2
1.5
1.3
1
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
42
56
67
64
65
27
46
51
48
58
40
28
47
54
70
50
76
58
56
61
52
values in the range from −2 to 0.3 were more efficient.
Increasing or decreasing pKa values beyond this range resulted
in gradual reducing yields. p-TSA and TFA were found to be
more effective, and p-TSA was considered to be the best choice
because of its operational simplicity.
The reactions of oxosulfonium ylides catalyzed by transition-
metals (Pd, Ru, Rh, Ir) are widely known to occur via the
carbenoid pathway. Therefore, in our investigated reaction, we
examined the additional use of Pd, Ru, or Rh-based catalysts
along with optimized conditions (Table 2B). However, none of
them provided an improved yield; rather, the yield was
significantly reduced. These indicate that the present reaction
undergoes via a noncarbenoid pathway.
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
1.3
1.3
1.3
1.3
1.3
1.3
1.3
1.3
1.3
1.3
1.3
1.3
1.3
1.3
1.3
La(OTf)3
Sc(OTf)3
Y(OTf)3
Yb(OTf)3
In(OTf)3
ZrCl4
BF3.OEt2
Cu(OAc)2
CuO
CuBr2
CuCl2
Cu(acac)2
Cu(BF4)2
CuCl
Table 2B. Evaluation of Transition Metal Catalysts
c
b
entry
catalyst in addition
time (h)
yield (%)
1
2
3
Pd2(dba)3
RuCl3
RhCl(PPh3)3
6
12
6
75
57
59
a
CuBr
Reaction conditions: 1 (1 mmol), 2 (1 mmol), and 3 (1 mmol), in
b
c
a
toluene at 80 °C (oil bath). Isolated yields. 10 mol %.
Substrates, reagents, and conditions: sulfoxonium ylide (1 mmol),
aldehyde and amine, Lewis acid, additive, reaction temp (oil bath).
b
Isolated yield obtained after carrying out the reaction for maximum
c
We surmised that, in the reaction, the dimethyl sulfoxide
byproduct is generated from sulfoxonium ylide, and it acted as
an oxidizing agent for dehydrogenative aromatization of the
dihydroimidazo[1,2-a]pyridine intermediate converting into
imidazo[1,2-a]pyridine (Scheme 2).25
Therefore, some experiments were performed to identify
whether an external oxidant would facilitate the dehydrogen-
ative aromatization and thus the reaction. Three sets of
experiments of the reaction were performed, under an O2
conversion in optimum time. p-TSA was not used.
An in situ process of the preparation of conjugated imine and
its reaction with ylide 1 was examined. After some initial
experiments, we found that a sequence of conversion of 2-
aminopyridine and 4-chlorobenzaldehyde to imine in toluene
(step i), electrophilic activation of imine by Cu(OTf)2 (step
ii), and subsequent reaction with the ylide (step iii) provided
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a common oxidant, with increased equivalence (0.1−1 equiv)
provided an inferior yield. All of these observations indicate
that dimethyl sulfoxide is most effective for dehydrogenative
aromatization to the fused imidazole ring, and therefore,
sulfoxonium ylide as its source is important for the annulation
reaction.
Scheme 2. Plausible Mechanism: Annulation and
Dehydrogenative Aromatization
Next, the substrate scope was explored. 2-Aminopyridines,
aldehydes, and β-ketosulfoxonium ylides with a variety of
electronically varied (withdrawing as well as donating) and
diverse substitutions were investigated in the reaction under
optimized conditions (Table 3).
Phenacylsulfoxonium ylides with Cl, F, OMe, and CF3
functionalities on the aromatic ring were examined (I−
XXIX). For all these investigated substrates, the reaction
proceeded smoothly and provided imidazo[1,2-a]-pyridines in
overall good yields. There was no significant electronic effect of
substitution motifs. Moreover, the nucleophilic (−OH) as well
environment, anhydrous aerobic oxygen (with CaCl2 guard
tube), and using K2S2O8 as an oxidant. However, these
oxidative conditions reduced the yield (Table S1). The
reaction using DMSO (anhydrous) solvent replacing toluene
also resulted in a reduced yield (Table S1). The use of CuCl2,
a
Table 3. Substrates Scope: Reactions with a Wide Range of Aldehydes, Azines, and Ylides
a
Reaction conditions: 1 (1 mmol), 2 (1 mmol), and 3 (1 mmol), in toluene at 80 °C (oil bath); 4 (isolated yields).
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as electrophilic (−CO2Et, −CN) functional moieties present in
the substrates were tolerated in the reaction (IX, XIII, and
XVIII). However, the reaction was not feasible for an aliphatic
acylsulfoxonium ylide or aliphatic aldehyde. Different classes of
heterocyclic-2-amidines, such as 2-aminopyrazine and 2-
aminopyrimidine, also proceeded with the reaction smoothly.
These enable access to dissimilar classes of N-fused imidazoles,
imidazo[1,2-a]-pyrazines, and pyrimidines. The compounds
that contain amidine functionality, such as benzamidine,
guanidine, and bis-guanide, were examined as substrates in
place of 2-aminoazine, but they did not undergo the reaction.
The conversion of these substrates into imine was found to be
nonsignificant. The developed experimental procedure was
found to be suitable for the gram-scale (12 mmol) reaction
without a significant decrease in yield for product I (76% vs
70%).
To gain insight into the mechanistic pathway, we analyzed
relevant results obtained in the optimization experiments and
also did some studies. Optimized conditions with additional
use of transition-metal (Pd, Rh, or Ru) catalysts provided a
reduced yield of the products, indicating that the reaction did
not undergo the carbenoid pathway. No external oxidant is
required. The reaction requires a Brønsted acid, p-TSA.
In the course of a reaction to the product (XII) under
optimized conditions, we isolated an intermediate (Q), which
is dihydro-imidazo[1,2-a]pyridine (Schemes 2 and S1). The
GC-MS study of the mixtures withdrawn at different intervals
of the progress of three sets of reactions using dissimilar
substrates was done. They clearly indicated the formation of
dimethyl sulfoxide as well as dimethylsulfide in the course of
the reaction. The HRMS study suggested the formation of
dihydro-imidazo[1,2-a]pyridine intermediate (P or its tauto-
meric form Q) and the imine (Scheme S1). The
phenacylsulfoxonium ylide is a 1,1-ambiphilic functional
motif similar to an α-halo-ester-α-deprotonated conjugated
base that undergoes Darzen glycidic ester condensation with
an aldehyde. However, in the present reaction, such
condensation did not take place since the α,β-epoxyketone
did not form, according to the HRMS study. Therefore, a
pathway that involves the reaction of a ylide with an aldehyde
to produce epoxyketone and its subsequent reaction with 2-AP
to form intermediate P or Q is ruled out. For dehydrogenation
of intermediate Q to the product, five sets of control
experiments were done (Table S2). The results indicate that
the combined role of CuCl2, DMSO, and TsOH is important.
On the basis of all of these results, a plausible mechanism has
been proposed (Scheme 2). The sulfoxonium ylide carbon
undergoes nucleophilic addition to aldimine. The intra-
molecular substitution with ring-N’s nucleophilic attack at α-
carbon of sulfonium-carbonyl and removal of dimethyl
sulfoxide forms annulated C−N bond. This produces a fused
imidazoline ring, intermediate P, which tautomerizes to
intermediate Q. Its dehydrogenative aromatization generates
imidazo[1,2-a]pyridine (Scheme 2).26
In conclusion, a method for the construction of the N-fused
imidazole motif by a new reaction of sulfoxonium ylides with
2-aminoazines and aldehydes has been developed. The
behavior of sulfoxonium ylides as a unique dual-purpose
substrate has been explored. It provides the ylidic carbon 1,1-
ambiphilic reactivity coupled with the source of an internal
oxidant, which promotes a formal pathway alternative to the
transition-metal carbenoid-based process of C−H activation−
functionalization and the insertion of ylidic carbon. This
behavior is important for new investigations. The present
method enables access to diverse N-fused imidazoles, which
are biologically important heterocycles, from easily available
substrates.
EXPERIMENTAL SECTION
■
General. All reagents (analytical grade) were used as purchased
without further purification. An oil bath was used for heating to carry
out reactions. Reactions were monitored by TLC, which was
performed using 0.2 mm precoated silica gel 60 F254 aluminum
sheets. Compounds were detected under a UV lamp. Column
chromatography was performed using silica gel (100−200 mesh,
ASTM). 1H NMR (400 or 500 MHz), 13C NMR (100 or 125 MHz),
and 19F NMR (470 MHz) spectra were recorded in CDCl3 or
DMSO-d6 on a Bruker Avance III spectrometer. The chemical shifts
have been reported in ppm using TMS/CFCl3 as an internal standard.
The multiplicity of the signals has been shown (s = singlet, d =
doublet, t = triplet, q = quartet, m = multiplet) with the coupling
constant (J value) expressed in hertz (Hz). High-resolution mass
spectroscopy (HRMS) spectra were obtained using electrospray
ionization (ESI) on time-of-flight (TOF) mass spectrometer XEVO
G2-XS QTOF equipment. Melting points were determined on a
melting point apparatus.
General Procedure for the Synthesis of N-Fused-Imidazoles
(Table 3). In a 25 mL two-necked round-bottom flask, heterocyclic
amidine (1 mmol, 1.3 equiv) and aldehyde (1 mmol, 1.3 equiv) were
taken. To this were added under argon toluene (anhydrous, 8 mL)
and 300 mg of 4 Å molecular sieves. The resulting mixture was
refluxed (120 °C, oil bath) and stirred for 2 h. The reaction was
allowed to cool down to 25 °C. CuCl2 (10 mol %) and p-TSA (10
mol %) were added. The resulting mixture was stirred at 25 °C for 10
min. Sulfoxonium ylide (1 mmol) was added, and the mixture was
stirred under argon at 80 °C. The reaction progress was monitored by
TLC. After completion of the reaction, the solvent was evaporated,
and water and ethyl acetate were added to the resultant slurry. The
layers were separated, the aqueous layer was washed with ethyl
acetate, and the organic layers were combined. The organic solution
was dried over anhydrous sodium sulfate (Na2SO4), filtered, and
evaporated to dryness. The crude mixture was subjected to normal
column chromatography over silica gel (100−200 mesh) using
EtOAc−hexanes (3:7) to afford the pure products.
Typical Procedure for the Gram-Scale Preparation of
Product I. For the gram-scale preparation of product I, the general
experimental procedure as described above has been followed with 2-
aminopyridine (1.13 g, 12 mmol), 4-chlorobenzaldehyde (1.7 g, 12
mmol), CuCl2 (160 mg, 1.2 mmol, 10 mol %), p-TSA (0.2 g, 1.2
mmol, 10 mol %), and ylide (1, 2.7 g, 12 mmol). The product I was
isolated in 3 g, 70% yield.
3-(4-Chlorobenzoyl)-2-(4-chlorophenyl)imidazo[1,2-a]pyridine
1
(I): light yellow solid; 278 mg, 76% yield, mp = 192−194 °C; H
The transformation pathway provides a formal [4+1]-
annulation with the sulfoxonium ylide functioning as a 1,1-
ambiphilic one-carbon synthon as well as a source of an
internal oxidant.27 It complements the process of a transition-
metal-catalyzed C−H activation−functionalization-based oxi-
dation. This dual role of the ylide demonstrates an unusual
pathway compared to common transition-metal-carbenoid
processes.
NMR (400 MHz, CDCl3) δ 9.50 (d, J = 6.9 Hz, 1H), 7.82 (d, J = 8.9
Hz, 1H), 7.56 (dd, J = 8.0 Hz, 7.6 Hz, 1H), 7.45 (d, J = 8.3 Hz, 2H),
7.27 (d, J = 8.4 Hz, 2H), 7.15−7.11 (m, 5H) ppm; 13C{1H} NMR
(100 MHz, CDCl3) δ 185.6, 153.5, 147.5, 138.4, 136.9, 134.9, 132.3,
131.4, 130.9, 129.6, 128.8, 128.2, 128.2, 119.8, 117.5, 114.9 ppm;
HRMS (ESI-TOF) m/z [M + H]+ calcd for C20H13Cl2N2O 367.0407,
found 367.0406.
3-(4-Chlorobenzoyl)-2-(4-bromophenyl)imidazo[1,2-a]pyridine
1
(II): light yellow solid; 258 mg, 63% yield, mp = 182−185 °C; H
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NMR (400 MHz, CDCl3) δ 9.50 (d, J = 6.9 Hz, 1H), 7.82 (d, J = 8.9
Hz, 1H), 7.57 (dd, J = 8.0 Hz, 7.8 Hz, 1H), 7.46 (d, J = 8.3 Hz, 2H),
7.30 (d, J = 8.3 Hz, 2H), 7.21 (d, J = 8.3 Hz, 2H), 7.15−7.12 (m, 3H)
ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 185.6, 153.6, 147.5, 138.5,
136.9, 132.8, 131.6, 131.1, 130.9, 129.6, 128.2, 123.2, 119.8, 117.6,
114.9 ppm; HRMS (ESI-TOF) m/z [M + H]+ calcd for
C20H13BrClN2O 410.9900, found 410.9901.
TOF) m/z [M + H]+ calcd for C20H14ClN2O2 349.0744, found
349.0737.
3-(4-Chlorobenzoyl)-2-(4-hydroxy-3,5-dimethoxyphenyl)-
imidazo[1,2-a]pyridine (X): yellow solid; 194 mg, 48% yield, mp >
200 °C; 1H NMR (400 MHz, CDCl3) δ 9.50 (d, J = 5.0 Hz, 1H), 7.82
(d, J = 7.2 Hz, 1H), 7.56 (d, J = 7.8 Hz, 3H), 7.17 (d, J = 8.1 Hz, 2H),
7.11 (dd, J = 6.7 Hz, 6.6 Hz, 1H), 6.65 (s, 2H), 3.73 (s, 6H) ppm;
13C{1H} NMR (100 MHz, CDCl3) δ 185.6, 154.6, 147.4, 146.7,
138.4, 137.3, 135.7, 130.9, 129.5, 128.2, 124.7, 119.4, 117.3, 114.7,
107.6, 97.9, 56.2 ppm; HRMS (ESI-TOF) m/z [M + H]+ calcd for
C22H18ClN2O4 409.0955, found 409.0956.
3-(4-Chlorobenzoyl)-2-(4-fluorophenyl)imidazo[1,2-a]pyridine
1
(III): brown solid; 210 mg, 66% yield, mp = 162−165 °C; H NMR
(500 MHz, CDCl3) δ 9.50 (d, J = 6.8 Hz, 1H), 7.79 (d, J = 8.8 Hz,
1H), 7.55 (dd, J = 7.5 Hz, 7.9 Hz, 1H), 7.43 (d, J = 8.4 Hz, 2H),
7.30−7.27 (m, 2H), 7.12−7.08 (m, 3H), 6.84 (t, J = 8.4 Hz, 2H)
ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 185.7, 162.9 (C−F, 1JC−F
= 246 Hz), 153.9, 147.5, 138.3, 136.9, 132.0, 131.9, 130.9, 130.0,
3-(4-Chlorobenzoyl)-2-(quinolin-3-yl)imidazo[1,2-a]pyridine (XI):
1
light yellow solid; 268 mg, 70% yield, mp = 186−189 °C; H NMR
(400 MHz, CDCl3) δ 9.60 (d, J = 6.8 Hz, 1H), 8.80 (s, 1H), 8.24 (s,
1H), 8.04 (d, J = 8.4 Hz, 1H), 7.90 (d, J = 8.9 Hz, 1H), 7.76−7.69
(m, 2H), 7.64 (dd, J = 8 Hz, 7.8 Hz, 1H), 7.56 (dd, J = 7.5 Hz, 7.4
Hz, 1H), 7.50 (d, J = 8.3 Hz, 2H), 7.20 (dd, J = 6.8 Hz, 6.9 Hz, 1H),
7.01 (d, J = 8.3 Hz, 2H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ
185.6, 150.8, 147.9, 147.2, 138.5, 137.0, 136.7, 130.8, 130.3, 129.9,
129.1, 128.4, 128.4, 127.9, 127.1, 127.0, 120.5, 117.6, 115.2 ppm;
HRMS (ESI-TOF) m/z [M + H]+ calcd for C23H15ClN3O 384.0904,
found 384.0901.
2
130.0, 129.6, 128.2, 128.2, 119.8, 117.5, 115.0 (C−F, JC−F = 21.7
Hz), 114.9 ppm; 19F NMR (470 MHz, CDCl3) δ −112.05 ppm;
HRMS (ESI-TOF) m/z [M + H]+ calcd for C20H13ClFN2O
351.0700, found 351.0698.
3-(4-Chlorobenzoyl)-2-(4-cyanophenyl)imidazo[1,2-a]pyridine
1
(IV): light yellow solid; 256 mg, 72% yield, mp = 185−187 °C; H
NMR (400 MHz, CDCl3) δ 9.49 (d, J = 6.9 Hz, 1H), 7.84 (d, J = 8.9
Hz, 1H), 7.60 (dd, J = 8.2 Hz, 7.5 Hz, 1H), 7.46 (m, 6H), 7.16 (m,
3H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 185.4, 152.3, 147.6,
138.9, 138.5, 136.7, 131.6, 130.9, 130.7, 129.9, 128.4, 128.2, 120.1,
118.4, 117.8, 115.4, 112.1 ppm. HRMS (ESI-TOF) m/z [M + H]+
calcd for C21H13ClN3O 358.0747, found 358.0739.
3-(4-Chlorobenzoyl)-2-(quinolin-4-yl)imidazo[1,2-a]pyridine
1
(XII): faint white solid; 153 mg, 40% yield, mp = 178−179 °C; H
NMR (400 MHz, DMSO-d6) δ 9.33 (d, J = 6.8 Hz, 1H), 8.41 (d, J =
4.3 Hz, 1H), 7.76 (d, J = 8.9 Hz, 1H), 7.72 (d, J = 8.4 Hz, 1H), 7.67
(d, J = 8.3 Hz, 1H), 7.57 (dd, J = 7.9, 7.5 Hz 1H), 7.51 (dd, J = 7.4,
7.3 Hz, 1H), 7.32 (dd, J = 8.3, 7.4 Hz, 1H), 7.20 (dd, J = 6.8, 6.7 Hz,
1H), 7.08 (d, J = 4.3 Hz, 1H), 6.99 (d, J = 8.2 Hz, 2H), 6.55 (d, J =
8.2 Hz, 2H) ppm; 13C{1H} NMR (100 MHz, DMSO-d6) δ 190.1,
155.6, 154.2, 152.5, 152.3, 145.2, 142.6, 141.1, 135.7, 135.0, 134.6,
134.1, 133.5, 132.2, 132.1, 131.3, 130.9, 128.7, 126.9, 122.6, 121.0
ppm; HRMS (ESI-TOF) m/z [M + H]+ calcd for C23H15ClN3O
384.0904, found 384.0910.
3-(4-Chlorobenzoyl)-2-(4-nitrophenyl)imidazo[1,2-a]pyridine
1
(V): light yellow solid; 236 mg, 63% yield, mp = 230−233 °C; H
NMR (400 MHz, CDCl3) δ 9.49 (d, J = 6.8 Hz, 1H), 8.04 (d, J = 8.4
Hz, 2H), 7.86 (d, J = 8.9 Hz, 1H), 7.62 (dd, J = 8 Hz, 7.8 Hz, 1H),
7.54 (d, J = 8.4 Hz, 2H), 7.49 (d, J = 8.2 Hz, 2H) 7.20−7.14 (m, 3H)
ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 185.3, 151.7, 147.6, 147.4,
140.4, 139.0, 136.8, 131.0, 130.9, 129.9, 128.4, 128.2, 123.0, 120.3,
117.8, 115.4 ppm; HRMS (ESI-TOF) m/z [M + H]+ calcd for
C20H13ClN3O3 378.0645, found 378.0642.
8-(Benzyloxy)-3-(4-chlorobenzoyl)-2-(4-cyanophenyl)imidazo-
[1,2-a]pyridine (XIII): brown solid; 253 mg, 56% yield, mp = 206−208
3-(4-Chlorobenzoyl)-2-(p-tolyl)imidazo[1,2-a]pyridine (VI): light
1
1
°C; H NMR (400 MHz, CDCl3) δ 9.04 (d, J = 6.8 Hz, 1H), 7.53−
yellow solid; 190 mg, 55% yield, mp = 167−169 °C; H NMR (400
7.50 (m, 4H), 7.47−7.34 (m, 7H), 7.14 (d, J = 8.4 Hz, 2H), 6.97 (dd,
J = 7.6, 7.0 Hz, 1H), 6.86 (d, J = 7.6 Hz, 1H), 5.46 (s, 2H) ppm;
13C{1H} NMR (100 MHz, CDCl3) δ 185.5, 151.2, 147.8, 141.9,
MHz, CDCl3) δ 9.53 (d, J = 6.9 Hz, 1H), 7.81 (d, J = 8.9 Hz, 1H),
7.54 (dd, J = 7.9 Hz, 7.8 Hz, 1H), 7.45 (d, J = 8.4 Hz, 2H), 7.21 (d, J
= 7.9 Hz, 2H), 7.12−7.07 (m, 3H), 6.95 (d, J = 7.8 Hz, 2H), 2.30 (s,
3H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 185.9, 155.3, 147.5,
138.7, 137.9, 137.1, 130.9, 130.8, 130.1, 129.4, 128.6, 128.2, 128.0,
119.7, 117.4, 114.6, 21.2 ppm; HRMS (ESI-TOF) m/z [M + H]+
calcd for C21H16ClN2O 347.0951, found 347.0956.
138.9, 138.4, 136.6, 135.6, 131.4, 130.9, 128.8, 128.3, 127.2, 121.0,
120.7, 118.4, 115.1, 111.9, 108.3, 71.1 ppm; HRMS (ESI-TOF) m/z
[M + H]+ calcd for C28H19ClN3O2 464.1166, found 464.1161.
3-(4-Methoxybenzoyl)-2-(4-methoxyphenyl)imidazo[1,2-a]-
pyridine (XIV): brown solid; 161 mg, 45% yield, mp = 198−200 °C;
1H NMR (400 MHz, CDCl3) δ 9.37 (d, J = 6.8 Hz, 1H), 7.76 (d, J =
8.0 Hz, 1H), 7.56 (d, J = 7.4 Hz, 2H), 7.47 (dd, J = 7.8, 7.8, 1H), 7.33
(d, J = 7.8 Hz, 2H), 7.03 (dd, J = 6.8, 6.8 Hz, 1H), 6.67 (d, J = 7.9 Hz,
2H), 6.64 (d, J = 7.5 Hz, 2H), 3.75 (s, 3H), 3.74 (s, 3H) ppm;
13C{1H} NMR (100 MHz, CDCl3) δ 186.2, 162.5, 159 6, 153.4,
3-(4-Chlorobenzoyl)-2-(4-methoxyphenyl)imidazo[1,2-a]-
pyridine (VII): light yellow solid; 256 mg, 71% yield, mp = 101−103
°C; 1H NMR (400 MHz, CDCl3) δ 9.55 (d, J = 6.9 Hz, 1H), 7.81 (d,
J = 8.9 Hz, 1H), 7.55 (dd, J = 7.4 Hz, 7.8 Hz 1H), 7.47 (d, J = 8.4 Hz,
2H), 7.26 (d, J = 8.7 Hz, 3H), 7.12−7.09 (m, 2H), 6.68 (d, J = 8.7
Hz, 2H), 3.56 (s, 3H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ
185.9, 160.1, 137.8, 137.1, 131.6, 130.9, 129.4, 128.3, 128.0, 126.1,
117.3, 114.6, 113.5, 55.4 ppm; HRMS (ESI-TOF) m/z [M + H]+
calcd for C21H16ClN2O2 363.0900, found 363.0908.
147.1, 131.9, 131.5, 131.1, 128.6, 127.9, 126.4, 119.6, 117.1, 114.0,
113.4, 113. 2, 55.3, 55.2 ppm; HRMS (ESI-TOF) m/z [M + H]+
calcd for C22H19N2O3 359.1396, found 359.1384.
3-(4-Chlorobenzoyl)-2-(3,4,5-trimethoxyphenyl)imidazo[1,2-a]-
pyridine (VIII): white solid; 350 mg, 83% yield, mp = 128−130 °C; 1H
NMR (400 MHz, CDCl3) δ 9.57 (d, J = 7.0 Hz, 1H), 7.84 (d, J = 8.9
Hz, 1H), 7.59 (ddd, J = 1.2 Hz, 8.3 Hz, 8.8 Hz, 1H), 7.51 (d, J = 8.5
Hz, 2H), 7.22−7.07 (m, 3H), 6.59 (s, 2H), 3.81 (s, 3H), 3.72 (s, 6H)
ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 185.6, 154.9, 152.8, 147.4,
138.9, 138.2, 137.4, 130.7, 129.6, 129.2, 128.3, 128.0, 119.7, 117.4,
114.9, 107.8, 61.1, 56.0 ppm; HRMS (ESI-TOF) m/z [M + H]+ calcd
for C23H20ClN2O4 423.1112, found 423.1115.
3-(4-Methoxybenzoyl)-2-(3,4,5-trimethoxyphenyl)imidazo[1,2-
a]pyridine (XV): off-white solid; 221 mg, 53% yield, mp = 125−127
°C; 1H NMR (400 MHz, CDCl3) δ 9.41 (d, J = 6.9 Hz, 1H), 7.80 (d,
J = 8.9 Hz, 1H), 7.61 (d, J = 8.8 Hz, 2H), 7.51 (ddd, J = 6.9, 6.8, 1.1,
1H), 7.08 (ddd, J = 6.9, 6.9, 1.0 Hz, 1H), 6.69−6.67 (m, 4H), 3.79 (s,
3H), 3.77 (s, 3H), 3.70 (s, 6H) ppm; 13C{1H} NMR (100 MHz,
CDCl3) δ 185.9, 162.9, 153.4, 152.7, 147.0, 138.3, 131.8, 131.3, 129.3,
128.8, 128.0, 119.8, 117.2, 114.3, 113.2, 107.6, 60.8, 55.9, 55.4 ppm;
HRMS (ESI-TOF) m/z [M + H]+ calcd for C24H23N2O5 419.1607,
found 419.1604.
6-Chloro-3-(4-methoxybenzoyl)-2-(4-cyanophenyl)imidazo[1,2-
a]pyridine (XVI): light yellow solid; 238 mg, 62% yield, mp = 198−
200 °C; 1H NMR (400 MHz, CDCl3) δ 9.40 (s, 1H), 7.74 (d, J = 9.4
Hz, 1H), 7.54−7.44 (m, 7H), 6.65 (d, J = 8.56, 2H), 3.79 (s, 3H)
ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 185.4, 163.5, 151.0, 145.5,
138.3, 132.0, 131.6, 130.6, 130.4, 130.2, 125.9, 123.2, 120.6, 118.5,
3-(4-Chlorobenzoyl)-2-(4-hydroxyphenyl)imidazo[1,2-a]pyridine
1
(IX): light yellow solid; 140 mg, 40% yield, mp = 191−192 °C; H
NMR (400 MHz, CDCl3) δ 9.53 (d, J = 5.9 Hz, 1H), 7.80 (d, J = 8.6
Hz, 1H), 7.58 (dd, 7.6 Hz, 7.6 Hz, 1H), 7.47 (d, J = 7.6 Hz, 2H), 7.13
(s, 5H), 6.55 (d, J = 7.0 Hz, 2H) ppm; 13C{1H} NMR (100 MHz,
CDCl3) δ 186.0, 157.6, 154.6, 147.2, 138.0, 136.9, 131.7, 131.0, 129.9,
128.3, 128.1, 124.5, 119.4, 116.8, 115.3, 114.9 ppm; HRMS (ESI-
5384
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The Journal of Organic Chemistry
pubs.acs.org/joc
Note
117.9, 113.5, 111.9, 55.5 ppm; HRMS (ESI-TOF) m/z [M + H]+
calcd for C22H15ClN3O2 388.0853, found 388.0849.
3-(4-Trifluoromethylbenzoyl)-2-(4-chlorophenyl)imidazo[1,2-a]-
pyridine (XXIIl): white solid; 304 mg, 76% yield, mp = 175−177 °C;
1H NMR (400 MHz, CDCl3) δ 9.66 (d, J = 6.9 Hz, 1H), 7.85 (d, J =
8-Methyl-3-(4-Methoxybenzoyl)-2-(naphthalen-1-yl)imidazo-
[1,2-a]pyridine (XVII): faint white solid; 235 mg, 60% yield, mp =
8.9 Hz, 1H), 7.63 (ddd, J = 1.2 Hz, 8.3 Hz, 8.8 Hz, 1H), 7.56 (d, J =
8.1 Hz, 2H), 7.40 (d, J = 8.1 Hz, 2H), 7.22−7.18 (m, 3H), 7.09−7.07
(m, 2H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 185.6, 154.7,
147.7, 141.8, 135.0, 132.9, 132.2, 131.3, 130.1, 129.6, 128.5, 128.0,
1
177−178 °C; H NMR (400 MHz, CDCl3) δ 9.45 (d, J = 6.8 Hz,
1H), 8.08−8.06 (m, 1H), 7.74−7.72 (m, 1H), 7.65 (d, J = 8.1, 1H),
7.46−7.41(m, 2H), 7.37 (d, J = 6.9 Hz, 1H), 7.30 (dd, J = 7.0, 1.1 Hz,
1H), 7.28−7.19 (m, 3H), 7.06 (dd, J = 6.9, 6.9 Hz, 1H), 6.18 (d, J =
8.8 Hz, 2H), 3.58 (s, 3H), 2.77 (s, 3H) ppm; 13C{1H} NMR (100
MHz, CDCl3) δ 186.5, 161.9, 152.7, 147.6, 133.4, 132.2, 132.1, 131.5,
130.6, 129.7, 128.6, 127.9, 127.8, 127.5, 126.3, 126.0, 125.7, 125.6,
124.7, 122.5, 114.5, 112.2, 55.1, 17.2 ppm; HRMS (ESI-TOF) m/z
[M + H]+ calcd for C26H21N2O2 393.1603, found 393.1598.
3
124.8 (C−F, JC−F = 3.73 Hz), 120.0, 117.6, 115.3 ppm; 19F NMR
(470 MHz, CDCl3) δ −63.01 ppm; HRMS (ESI-TOF) m/z [M +
H]+ calcd for C21H13ClF3N2O 401.0669, found 401.0667.
3-(4-Trifluoromethylbenzoyl)-2-(3,4,5-trimethoxyphenyl)-
imidazo[1,2-a]pyridine (XXIV): light yellow solid; 282 mg, 62% yield,
1
mp = 108−109 °C; H NMR (400 MHz, CDCl3) δ 9.65 (d, J = 6.9
7-Methyl-carboxylate-3-(4-methoxybenzoyl)-2-(quinolin-3-yl)-
Hz, 1H), 7.85 (d, J = 8.9 Hz, 1H), 7.66−7.59 (m, 3H), 7.44 (d, J =
8.2 Hz, 2H), 7.17(ddd, J = 6.9, 6.9, 1.8 Hz, 1H), 6.54(s, 2H), 3.74 (s,
3H), 3.68 (s, 6H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 185.3,
155.5, 152.7, 147.6, 142.1, 138.8, 133.1 (C−F, 2JC−F = 32 Hz), 130.0,
imidazo[1,2-a]pyridine (XVIII): yellow solid; 178 mg, 41% yield, mp
1
= 180−183 °C; H NMR (400 MHz, CDCl3) δ 9.37 (d, J = 7.2 Hz,
1H), 8.89 (d, J = 2.0 Hz, 1H), 8.53 (s, 1H), 8.31 (d, J = 1.7 Hz, 1H),
8.02 (d, J = 8.8 Hz, 1H), 7.72−7.65 (m, 3H), 7.61 (d, J = 8.8 Hz,
2H), 7.52 (dd, J = 7.5 Hz, 6.9 Hz, 1H), 6.55 (d, J = 8.8 Hz, 2H), 4.04
(s, 3H), 3.57 (s, 3H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ
185.8, 164.9, 163.4, 150.9, 150.8, 147.2, 146.5, 136.9, 132.1, 130.2,
130.1, 130.0, 129.1, 128.1, 127.6, 127.2, 126.9, 126.8, 121.5, 119.7,
113.7, 113.6, 55.3, 52.9 ppm; HRMS (ESI-TOF) m/z [M + H]+ calcd
for C26H20N3O4 438.1454, found 438.1458.
3
1
129.8, 129.5, 128.4, 124.6 (C−F, JC−F = 3 Hz) 124.4 (C−F, JC−F
=
271 Hz) 122.0, 119.6, 117.4, 115.1, 107.7, 60.7, 56.0 ppm; 19F NMR
(470 MHz, CDCl3) δ −63.01 ppm; HRMS (ESI-TOF) m/z [M +
H]+ calcd for C24H20F3N2O4 457.1375, found 457.1379.
6 - B r o m o - 3 - ( 4 - t r i fl u o r o m e t h y l b e n z o y l ) - 2 - ( 3 , 4 , 5 -
trimethoxyphenyl)imidazo[1,2-a]pyridine (XXV): yellow solid; 234
1
mg, 44% yield, mp = 162−164 °C; H NMR (500 MHz, CDCl3) δ
3-(4-Fluorobenzoyl)-2-(4-fluorophenyl)imidazo[1,2-a]pyridine
9.81 (s, 1H), 7.73 (d, J = 9.36 Hz, 1H), 7.69−7.64 (m, 3H), 7.46 (d, J
= 8.0 Hz, 2H), 6.52 (s, 2H), 3.75 (s, 3H), 3.68 (s, 6H) ppm; 13C{1H}
NMR (125 MHz, CDCl3) δ 185.4, 155.5, 152.9, 146.0, 141.7, 139.2,
1
(XIX): light yellow solid; 213 mg, 64% yield, mp = 116−119 °C; H
NMR (500 MHz, CDCl3) δ 9.47(d, J = 6.9 Hz, 1H), 7.82 (d, J = 8.7
Hz, 1H), 7.55−7.50 (m, 3H), 7.31−7.28 (m, 2H), 7.11−7.08 (m,
1H), 6.84−6.78 (m, 4H), ppm; 13C{1H} NMR (100 MHz, CDCl3) δ
3
133.6, 133.3, 133.2, 129.6, 128.5, 124.7 (C−F, JC−F = 3.57 Hz),
122.0, 119.8, 118.0, 109.9, 107.8, 60.8, 56.1 ppm; 19F NMR (470
MHz, CDCl3) δ −63.01 ppm; HRMS (ESI-TOF) m/z [M + H]+
calcd for C24H19BrF3N2O4 535.0480, found 535.0481.
1
1
185.5, 164.9 (C−F, JC−F = 252 Hz), 162.8 (C−F, JC−F = 248 Hz),
153.6, 147.4, 134.8 (C−F, 4JC−F = 3 Hz), 132.0 (C−F, 3JC−F = 9 Hz),
3
4
131.9 (d, C−F, JC−F = 8 Hz), 130.0 (C−F, JC−F = 3 Hz), 129.4,
6-Methyl-3-(4-trifluoromethylbenzoyl)-2-(quinolin-3-yl)imidazo-
2
128.2, 119.7, 117.4, 115.0 (d, C−F, JC−F = 22 Hz), 115.0 (C−F,
[1,2-a]pyridine (XXVI): light yellow solid; 260 mg, 60% yield, mp =
2JC−F = 22 Hz), 114.8 ppm; 19F NMR (470 MHz, CDCl3) δ −105.84,
1
179−181 °C; H NMR (500 MHz, CDCl3) δ 9.50 (s, 1H), 8.73 (s,
−112.32 ppm; HRMS (ESI-TOF) m/z [M + H]+ calcd for
C20H13F2N2O 335.0996, found 335.0995.
1H), 8.03 (s, 1H), 7.95 (d, J = 10 Hz, 1H), 7.76 (s, 1H), 7.67 (dd, J =
10, 5 Hz, 1H), 7.57 (d, J = 5 Hz, 1H), 7.52 (d, J = 5 Hz, 2H), 7.47
(dd, J = 10, 5 Hz, 2H), 7.18 (d, J = 10 Hz, 2H), 2.47 (s, 3H) ppm
13C{1H} NMR (125 MHz, CDCl3) δ 185.5, 150.5, 147.2, 141.8,
136.9, 133.2, 130.3, 132.8, 130.3, 129.5 (C−F, 2JC−F = 48 Hz), 127.7,
127.1, 126.6, 125.8, 124.9 (C−F, 3JC−F = 2.97 Hz), 124.2 (C−F, 1JC−F
= 271 Hz), 122.0, 116.9, 18.6 ppm; 19F NMR (470 MHz, CDCl3) δ
−63.49 ppm; HRMS (ESI-TOF) m/z [M + H]+ calcd for
C25H17F3N3O 432.1324, found 432.1321.
8-(Benzyloxy)-3-(4-fluorobenzoyl)-2-(4-chlorophenyl)imidazo-
[1,2-a]pyridine (XX): light yellow solid; 166 mg, 37% yield, mp =
1
196−198 °C; H NMR (400 MHz, CDCl3) δ 9.04 (d, J = 6.8 Hz,
1H), 7.58−7.52 (m, 4H), 7.41 (dd, J = 7.0 Hz, 7.5 Hz, 2H), 7.37−
7.33 (m, 3H), 7.13 (d, J = 8.4 Hz, 2H), 6.93 (dd, J = 7.5 Hz, 7.2 Hz,
1H), 6.87−6.82 (m, 3H), 5.48 (s, 2H) ppm; 13C{1H} NMR (100
1
MHz, CDCl3) δ 185.7, 165.0 (C−F, JC−F = 253 Hz), 152.2, 147.6,
141.8, 135.8, 134.7, 134.6, 132.4, 132.1, 132.0, 131.6, 128.8, 128.3,
2
3-(4-Chlorobenzoyl)-2-(4-chlorophenyl)imidazo[1,2-a]pyrazine
128.0, 127.2, 120.8, 120.7, 115.1 (C−F, JC−F = 21.1 Hz), 114.6,
1
(XXVII): brown solid; 150 mg, 41% yield, mp = 152−155 °C; H
108.1, 71.1 ppm; 19F NMR (470 MHz, CDCl3) δ −105.94 ppm;
HRMS (ESI-TOF) m/z [M + H]+ calcd for C27H19ClFN2O2
457.1119, found 457.1113.
NMR (400 MHz, CDCl3) δ 9.33 (s, 1H), 9.19 (d, J = 4.4 Hz, 1H),
8.22 (d, J = 4.5 Hz, 1H), 7.50 (d, J = 8.3 Hz, 2H), 7.33 (d, J = 8.3 Hz,
2H), 7.19 (d, J = 8.3 Hz, 4H) ppm; 13C{1H} NMR (100 MHz,
CDCl3) δ 185.9, 152.9, 143.9, 141.5, 139.5, 135.7, 135.6, 132.3, 131.4,
131.3, 130.9, 128.6, 128.5, 120.1 ppm; HRMS (ESI-TOF) m/z [M +
H]+ calcd for C19H12Cl2N3O 368.0357, found 368.0351.
8-Methyl-3-(4-fluorobenzoyl)-2-(4-methoxyphenyl)imidazo[1,2-
a]pyridine (XXI): light yellow solid; 262 mg, 73% yield, mp = 164−
1
166 °C; H NMR (400 MHz, CDCl3) δ 9.37 (d, J = 6.8 Hz, 1H),
7.56−7.52 (m, 2H), 7.34−7.27 (m, 3H), 7.00 (dd, J = 6.9, 6.9, 1H),
6.81 (dd, J = 8.6, 8.6 Hz, 2H), 6.67 (d, J = 8.7 Hz, 2H), 3.76 (s, 3H),
2.74 (s, 3H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 185.8, 164.6
3-(4-Methoxybenzoyl)-2-(4-chlorophenyl)imidazo[1,2-a]-
pyrazine (XXVIII): brown solid; 145 mg, 40% yield, mp = 192−195
°C; 1H NMR (400 MHz, CDCl3) δ 9.35 (s, 1H), 9.95 (d, J = 4.4 Hz,
1H), 8.18 (d, J = 4.6 Hz, 1H), 7.57 (d, J = 8.5 Hz, 2H), 7.43 (d, J =
8.2 Hz, 2H), 7.29 (d, J = 8.2 Hz, 2H), 6.80 (d, J = 8.6 Hz, 2H), 3.75
(s, 3H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 185.7, 163.6,
150.6, 143.3, 141.1, 133.9, 132.5, 132.4, 131.9, 131.8, 130.1, 128.5,
120.66, 120.60, 114.0, 56.0, ppm; HRMS (ESI-TOF) m/z [M + H]+
calcd for C20H15ClN3O2 364.0853, found 364.0850.
1
4
(C−F, JC−F = 252 Hz), 159 8, 154.3, 147.3, 135.1 (C−F, JC−F = 3
3
Hz), 132.0 (C−F, JC−F = 9 Hz), 131.6, 128.1, 127.3, 126.5, 125.8,
120.0, 114.8 (C−F, 2JC−F = 22 Hz), 114.5, 113.4, 55.3, 17.1 ppm; 19
F
NMR (470 MHz, CDCl3) δ −112.30 ppm; HRMS (ESI-TOF) m/z
[M + H]+ calcd for C22H18FN2O2 361.1352, found 361.1350.
3-(4-Fluorobenzoyl)-2-(3,4,5-trimethoxyphenyl)imidazo[1,2-a]-
pyridine (XXII): faint white, solid; 263 mg, 65% yield, mp = 142−144
°C; 1H NMR (400 MHz, CDCl3) δ 9.51 (d, J = 6.8 Hz, 1H), 7.82 (d,
J = 8.9 Hz, 1H), 7.62−7.54 (m, 3H), 7.12 (dd, J = 6.8, 5.9, 1H), 6.85
(dd, J = 8.6, 8.4 Hz, 2H), 6.59 (s, 2H), 3.78 (s, 3H), 2.71 (s, 6H)
ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 185.5, 164.8 (C−F, 1JC−F
3-(4-Chlorobenzoyl)-2-(4-Chlorophenyl)imidazo[1,2-a]-
pyrimidine (XXIX): faint white solid; 103 mg, 28% yield, mp = 157−
1
159 °C; H NMR (400 MHz, CDCl3) δ 8.74 (d, J = 1.8 Hz, 1H),
8.41−8.36 (m, 3H), 7.57 (d, J = 8.5 Hz, 2H), 7.52 (d, J = 8.4, 2H),
7.47 (d, J = 8.5 Hz, 2H), 7.00−6.98 (m, 1H) ppm; 13C{1H} NMR
(100 MHz, CDCl3) δ 187.7, 152.3, 146.6, 140.4, 139.5, 136.0, 135.4,
132.6, 131.8, 131.7, 129.5, 128.5, 126.6, 125.5, 110.3 ppm; HRMS
(ESI-TOF) m/z [M + H]+ calcd for C19H12Cl2N3O 368.0357, found
368.0363.
4
= 252 Hz), 154.5, 152.8, 147.3, 138.7, 135.1 (C−F, JC−F = 3 Hz),
3
131.8 (C−F, JC−F = 9 Hz), 129.4, 129.2, 128.2 119.7, 117.4, 114.9
2
(C−F, JC−F = 22 Hz), 114.7, 107.7, 60.9, 56.0 ppm; 19F NMR (470
MHz, CDCl3) δ −106.34 ppm; HRMS (ESI-TOF) m/z [M + H]+
calcd for C23H20FN2O4 407.1407, found 407.1413.
5385
https://doi.org/10.1021/acs.joc.1c00052
J. Org. Chem. 2021, 86, 5380−5387

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
Zhou, X.; Zheng, G.; Li, X. Sulfoxonium Ylides as a Carbene
Precursor in Rh(III)-Catalyzed C-H Acylmethylation of Arenes. Org.
Lett. 2017, 19, 5256−5259. (d) Mangion, I. K.; Nwamba, I. K.;
Shevlin, M.; Huffman, M. A. Iridium-Catalyzed X-H Insertions of
Sulfoxonium Ylides. Org. Lett. 2009, 11, 3566. (e) Mangion, I. K.;
Weisel, M. Gold (I) catalysis of X-H bond insertions. Tetrahedron
Lett. 2010, 51, 5490−5492.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00052.
■
sı
Additional experiments and H and 13C NMR spectra
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AUTHOR INFORMATION
Corresponding Author
Sankar K. Guchhait − Department of Medicinal Chemistry,
National Institute of Pharmaceutical Education and Research
(NIPER), Mohali, Punjab 160062, India; orcid.org/
0000-0002-1817-2172; Email: skguchhait@niper.ac.in
■
Authors
Meenu Saini − Department of Medicinal Chemistry, National
Institute of Pharmaceutical Education and Research
(NIPER), Mohali, Punjab 160062, India
Viren J. Khivsara − Department of Medicinal Chemistry,
National Institute of Pharmaceutical Education and
Research (NIPER), Mohali, Punjab 160062, India
Santosh K. Giri − Department of Medicinal Chemistry,
National Institute of Pharmaceutical Education and
Research (NIPER), Mohali, Punjab 160062, India
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00052
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge financial support from SERB, New
Delhi, for this investigation. M.S. is thankful to UGC for a
fellowship.
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