Preparation and Synthetic Applicability of Imidazole-Containing Cyclic Iodonium Salts

Article abstract of DOI:10.1021/acs.joc.1c00483

A novel approach to the preparation of imidazole-substituted cyclic iodonium salts has been developed via the oxidative cyclization of 1-phenyl-5-iodoimidazole using a cheap and available Oxone/H2SO4 oxidative system. The structure of the new polycyclic heteroarenes has been confirmed by single-crystal X-ray diffractometry, revealing the characteristic structure features for cyclic iodonium salts. The newly produced imidazole-flanked cyclic iodonium compounds were found to readily engage in a heterocyclization reaction with elemental sulfur, affording benzo[5,1-b]imidazothiazoles in good yields.

Full text of DOI:10.1021/acs.joc.1c00483

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Article
Preparation and Synthetic Applicability of Imidazole-Containing
Cyclic Iodonium Salts
Nikita S. Antonkin, Yulia A. Vlasenko, Akira Yoshimura, Vladimir I. Smirnov, Tatyana N. Borodina,
Viktor V. Zhdankin, Mekhman S. Yusubov,* Alexandr Shafir,* and Pavel S. Postnikov*
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ABSTRACT: A novel approach to the preparation of imidazole-substituted cyclic iodonium salts has been developed via the
oxidative cyclization of 1-phenyl-5-iodoimidazole using a cheap and available Oxone/H2SO4 oxidative system. The structure of the
new polycyclic heteroarenes has been confirmed by single-crystal X-ray diffractometry, revealing the characteristic structure features
for cyclic iodonium salts. The newly produced imidazole-flanked cyclic iodonium compounds were found to readily engage in a
heterocyclization reaction with elemental sulfur, affording benzo[5,1-b]imidazothiazoles in good yields.
Despite the promising synthetic applicability of CISs, their
potentially wider usage is still contingent upon the chemical
community resolving a series of issues and challenges. For
example, the evaluation of the structure and properties of such
cyclic salts has been centered on the simpler carbocyclic scaffold
A,5 with its heterocycle-flanked congeners still relatively
unexplored. The first examples of pyridine and quinolone
substituted iodonium salts B (Figure 1, a) were reported by the
Detert laboratory.10 Shortly after, Wen and co-workers prepared
a wide range of heterocyclic CISs containing chromone and
thiochromone moieties C (Figure 1, a) and explored their
synthetic potential as entry points to polycyclic cores.6a,11
Indeed, the oxidation of iodoarenes bearing six-membered
heterocyclic moieties appears to proceed more readily than that
of those bearing five-membered electron-rich heterocycles. For
this reason, the CISs based on thiophene and furan have been
implemented as their benzo-conjugated derivatives D (Figure 1,
a).6f,g,12 Only a few examples exist of CIS' embedding five-
membered electron-rich heterocycles, probably as a result of
non-straightforward methods for the preparation of the
necessary precursors, and the sensitivity of such heterocyclic
INTRODUCTION
■
Currently, the chemistry of hypervalent compounds has proven
to be one of the fast-growing fields of organic chemistry.1
Indeed, the λ3-iodanes have found widespread applications in a
variety of organic transformations, most commonly as
oxidants1,2 and group-transfer reagents.3 Among these, one of
the most applicable classes of iodine(III) derivatives are the so-
called diaryliodonium salts, whose structure bears two carbon-
centered aryl ligands bound to a central iodine atom. This latter
compound class is often used as a convenient type of
electrophilic synthons.4
In the last 10 years, there has been a particular resurgence of
interest in cyclic iodonium salts (CIS), which are characterized
by the presence of two electrophilic carbon centers in a rigid,
normally tricyclic structure (Figure 1).5 This structure and the
unique reactivity of such substances have allowed for their direct
transformation into various carbo- and heterocycles via
innovative synthetic sequences. Thus, very recently, a range of
useful synthetic methods have been developed including the
transformation of CIS into sulfur- and nitrogen-containing
heterocycles,6 carbocyclization,7 as well as processes for the
selective ring-opening via the C−I bond cleavage, including an
interesting enantioselective variant.8 In fact, such hetero- and
carbocyclizations processes are gaining prominence as powerful
tools for accessing fused cyclic building blocks. In addition, a
very recent development in this area involves the ability of cyclic
iodonium salts also to act as a new class of halogen-bonding
catalysts.9
Received: March 2, 2021
Published: May 4, 2021
https://doi.org/10.1021/acs.joc.1c00483
© 2021 American Chemical Society
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Figure 1. Examples of known cyclic iodonium salts.
cores to the conditions commonly employed in C-I
oxidation.12,13 Only recently, the Nachtsheim group developed
a facile approach to the preparation of iodine-containing
heterocycles flanked by a pyrazole moieties E (Figure 1, b).14
In this context, we recently proposed a novel method for the
synthesis of 1-aryl-5-iodoimidazoles, which may be construed as
a promising substrate class for the formation of heterocycle-
flanked cyclic iodonium salts. In order to explore the synthetic
potential of such reagents, in this contribution, we have
developed a method for the preparation of cyclic iodonium
salts containing the imidazolyl moiety. We also go on to
showcase the synthetic applicability of such salts in the synthesis
of conjugated thienoimidazoles.
Table 1. Optimization of the Conditions
entry oxidant
additive/medium
temp
time [h] yield [%]
a
1
2
3
4
5
6
mCPBA p-TsOH, TFE
mCPBA TfOH, TFE
mCPBA TfOH, DCE
mCPBA AcOH
r.t.
r.t.
50 °C
r.t.
r.t.
125 °C
24
24
65
24
24
2
0
0
0
0
0
0
a
a
Bleach
NaIO4
AcOH
NaOAc, Ac2O,
AcOH
b
RESULTS AND DISCUSSION
■
7
8
9
NaBO3
Oxone
Oxone
AcOH
H2SO4
H2SO4
50 °C
0 °C to r.t.
0 °C to r.t.
24
2
2
0
50
84
cd
,
As mentioned above, we envisioned accessing the imidazole-
flanked cyclic iodonium salt family 3 via a two-step sequence
involving an initial evolution of the iodonium salt 1 via Cu-
catalyzed internal N-arylation, followed by an oxidative
cyclization of the resulting 5-iodo-N-aryl imidazole 2 (Figure
1, c). Given that the initial Cu-catalyzed aryl transfer step had
been studied in our prior study, we initially focused on
identifying conditions for efficient oxidation of the iodine
atom in the model 1-phenyl-5-iodoimidazole 2a (Table 1). The
early experiments revealed that the facile protonation of the ring
nitrogen atoms under the acidic conditions, commonly
employed in organo-iodine oxidation processes, strongly
influenced the reactivity of 2. Indeed, the previously reported
methods involving m-CPBA as oxidant in the presence of strong
acids did not result in the formation of desired hypervalent
iodine species (entries 1−3, Table 1).10,15 Thus, in the case of p-
toluenesulfonic or trifluoromethanesulfonic acid, only the
corresponding protonated imidazolium salts were obtained,
even at elevated temperature14 (entries 1−3). This result
highlights the challenge of achieving the oxidative cyclization in
de
,
a
b
Protonated 2a was isolated. Deiodination process occurred.
c
Isolation by precipitation with water, product was isolated as
d
−HSO4 salt. Reaction conditions:1-phenyl-5-iodoimidazole 2a (0.5
mmol), Oxone (0.325 mmol) in H2SO4 (0.8 mL) from 0 °C to r.t.
e
over 2 h. Isolation by precipitation with 9 M NaOH solution.
this system, given that the protonation of the imidazole nitrogen
is expected to deactivate the iodine toward oxidation. With that
in mind, we tested the oxidative systems based on weaker acids,
such as AcOH in the presence of m-CPBA, NaBO3, NaIO4 as
well as bleach (entries 4−7). Unfortunately, we did not observe
the formation of desired iodonium salt 3a.
These poor initial results led us to consider persulfate-based
oxidant systems, in particular, the well-behaved Oxone reagent.
Indeed, the Oxone/H2SO4 combination is known to be efficient
in the preparation of cyclic or noncyclic iodonium salts.16 In our
case, an addition of the finely ground Oxone (i.e., the triple salt
KHSO5·0.5KHSO4·0.5K2SO4) to the solution of the iodoimi-
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a
Scheme 1. Synthesis of Benzo[d]imidazo[5,1-b][1,3]iodazol-4-ium Derivatives 3a−3q
a
b
Reaction conditions: 1-aryl-5-iodoimidazole 2 (0.5 mmol), Oxone (0.325 mmol) in H2SO4 (0.8 mL) from 0 °C to r.t. Yield for 2 mmol scale.
c
d
e
Increased amount of Oxone. Amount of reagents was scaled down (see Experimental Section). Isolation by addition of KI.
dazole 2a in H2SO4 under vigorous stirring led to the full
consumption of starting material after 2 h. A subsequent
addition of water led to the precipitation of the desired product
3a in 50% yield as a hydrogen sulfate salt. Suspecting incomplete
product precipitation due to a partial solubility of iodonium
hydrogen sulfates in water, we repeated the experiment with the
addition of Na2CO3 at the isolation stage. This modification led
to the isolation of the corresponding hydroxide form in 89%
yield. Unfortunately, the extremely low solubility of this −OH
species did not allow us to use common NMR spectroscopy for
its structural characterization. Through a final round of
optimization, the target 3a-HSO4 was isolated in 84% via the
addition of a 9 M solution of NaOH so as to reach a pH value of
4−5. This form of the product is now readily soluble in DMSO
and, to a lesser extent, in water and MeOH, and was used as a
substrate for the further transformations.
straightforward method for accessing N-substituted imidazoles
bearing iodine in the 5-position. In the context of the current
study, the oxidation of 1-aryl-5-iodoimidazoles containing
electron-donating groups on the aromatic ring, via the
previously optimized procedure, proceeded smoothly to give
corresponding iodonium salts 3f, 3h, and 3i in high yields.
Under these conditions, halogen-substituted precursors (2c−
2e, 2g, 2j, 2l, 2o) also underwent the oxidative cyclization. For
the latter substrate class, the initial runs led to the desired
iodonium salts being obtained in somewhat lower yields due to
incomplete conversion of starting material. Nevertheless, the
addition of a second portion of Oxone and sulfuric acid led to the
full consumption of starting iodide 2 with the formation of target
products with meaningful yields (see products 3c−3e, 3g, 3j, 3l,
3o). The oxidation of the C-I unit was found to be sensitive to
the steric hindrance at both the imidazole and the N-aryl rings.
Thus, the 1-aryl-5-iodoimidazoles 2j−2l containing a sub-
stituent in the o-position of the phenyl ring gave an ∼60% yield
of the target iodonium salts 3j−3l independently of the
electronic effects. It should be noted that, although two isomeric
products are possible for the meta-substituted N-aryl precursors
2g−2i, the process provided for a selective formation of species
With the optimal conditions in hand, we sought to
demonstrate the synthetic applicability of this approach in a
broader range of 1-aryl-5-iodoimidazoles (Scheme 1). As
mentioned earlier, a series of substituted 1-aryl-5-iodoimida-
zoles have been prepared previously via a Cu-catalyzed
intramolecular N-arylation,17 with the method representing a
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3g−3i with the new C-I para to the N-Ar substituent group, with
the NMR of the crude reaction mixture revealing less than 2% of
the isomer. This selectivity is likely governed by steric factors
and is also in line with the Electrophilic Aromatic Substitution
preferences (SEAr) of the iodination step. It will be interesting to
establish whether this lower efficiency stems from the steric
hindrance of the 2-Me substituent hindering attainment of the
necessary co-planarity en route the final cyclic structure. Indeed,
application of a strong oxidative system did not allow for the
preparation of the cyclic iodonium salts from 1-aryl-5-
iodoimidazoles containing electron-rich N-(hetero)aryl sub-
stituents, such as the naphthyl, the 4-methoxyphenyl, or the 2-
thienyl group. In all such cases, a complete consumption of
starting material was accompanied by the formation of a rather
intractable mixture, likely the result of an over-oxidation.
In some cases, the solubility of the final −HSO4 iodonium salts
was a critical factor in their isolation and characterization. For
instance, the iodonium species 3q had to be isolated as its iodide
salt due to the high solubility of the corresponding hydrogen
sulfate form in water. In contrast, for product 3p, the hydrogen
sulfate form had a very low solubility in DMSO and other
common solvents, to the point of making its characterization by
NMR a challenge.
Crystals suitable for X-ray study were grown from the water
solution of salts 3c and 3j in their sulfate form via slow
evaporation. The 3c was found to crystallize in a dimeric
structural motif formed by short contacts between the
hypervalent iodine centers and the and oxygen atoms of the
sulfate anions (I1−O3 (2.559 and 3.330 Å)) (Figure 2).
Additionally, the iodine atoms form close contacts with
neighboring O4 atoms of sulfates (I1−O4 (2.552 Å)), which
can be considered as yet another example of bifurcated two-
centered halogen bonds.18 The first coordination sphere of
hypervalent iodine centers in 3c is close to square planar
geometry, as attested to by the CCOO torsion angle, i.e., O(3)−
O(4)−C(1)−C(7), of 4.35°. Generally, the crystal structure of
3c is in a good agreement with those published previously, such
as carbocyclic iodonium salts.16a,18,19
The iodonium salt 3j formed a more complicated structural
motif due to the incorporation of water (Figure 3) and the
appearance of additional π-stacking interactions between the
aryl and the heteroaryl rings, with the distance between
centroids Cg2 (imidazole ring) and Cg1 (benzene ring) of
3.550 Å. Thus, the iodonium cations formed the infinite chains
connected by sulfate anions via short contacts of iodine atoms
and oxygen atoms (I1−O3 (2.668 Å); I1−O2 (3.314 Å); I2−O4
(2.557 Å)). Surprisingly, for the iodine I1, we observed a contact
with water molecule (2.95 Å), which replaces the interaction
Figure 2. X-ray crystal structure of 3c showing the dimeric nature of the
cyclic iodonium salt. Selective distances and angles: C1−I1 = 2.122(2)
Å, C7−I1 = 2.077(2) Å, C1−C6 = 1.394(2) Å, C6−N2 = 1.408(3) Å,
C7−N2 = 1.388(2) Å, ∠C1−I1−C7 = 80.25(8)°, ∠I1−C7−C8−H8 =
−5.0°. The molecular structure is represented by thermal vibration
ellipsoids of 50% probability.
Figure 3. Crystal structure of 3j showing the dimeric nature of the cyclic iodonium salt. Selective distances and angles: I1−C3 = 2.105(2) Å, I1−C4 =
2.058(2) Å, C3−C7 = 1.400(3) Å, C4−N1AA = 1.389(3) Å, C7−N1AA = 1.418(3) Å, ∠C3−I1−C4 = 80.23(8)°, ∠I1−C4 −C5−H5 = 4.5°, I2−C17
= 2.078(2) Å, I2−C18 = 2.118(2) Å. Inter-stacking interactions between iodonium salts: distance between centroids Cg1−Cg2 = 3.550 Å. The
molecular structure is represented by thermal vibration ellipsoids of 50% probability.
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with the sulfate anion observed for 3c. The other water
molecules formed the hydrogen bonds with sulfate anions (2.04
and 2.13 Å).
In the next step, we sought to demonstrate the synthetic
applicability of newly formed iodonium salts in a heterocycle-
forming process, specifically through the use of elemental sulfur
under basic conditions.12 Such heterocyclizations ought to
provide a novel method for the synthesis of benzo[5,1-
b]imidazothiazoles (Scheme 2), which have wide application
of the target product 4 did not show a clear dependence on the
electronic nature of the N-aryl moiety. A slight decrease in yield
was observed for the ortho-substituted iodonium salts,
presumably due to steric hindrance.
Surprisingly, the iodonium salts 3m, 3n, 3q bearing a
substituent on the imidazolyl moiety were reluctant to undergo
the heterocyclization under such conditions, with only the
reduction products, i.e., the corresponding 1-aryl-5-iodoimida-
zoles, isolated from such attempts. A related behavior was also
observed for salts 3j and 3l. For these, the desired benzo[5,1-
b]imidazothiazoles were indeed detected by GC−MS chroma-
tography, but the presence of the reduced iodonium salts
impurities hampered their isolation in a pure form.
Scheme 2. Synthesis of Benzo[5,1-b]imidazothiazoles 4a−
a
4k
CONCLUSION
■
In conclusion, we have described a method for the preparation of
a novel series of heterocycle-fused benzo[d]imidazo[5,1-b]-
[1,3]iodazol-4-ium salts. The synthetic procedure includes the
oxidation of 1-aryl-5-iodoimidazoles by a cheap and readily
available Oxone in sulfuric acid medium, followed by a
straightforward precipitation of the desired compounds by
NaOH. The crystal structures of two representative compounds,
in their sulfate form, revealed the typical dimeric structure for
cyclic iodonium cations coordinated by two sulfate anions. The
newly formed cyclic iodonium salts were well-suited as a
platform core for a subsequent heterocyclization with elemental
sulfur, with the formation of benzo[5,1-b]imidazothiazoles
taking place with with good to high yields. We believe that
this study, in addition to expanding our understanding of the
formation and reactivity of heterocycle-containing cyclic
iodonium species, also opens the door to further methods
development, especially in the utilization of λ3-iodane for the
synthesis of heteroatom-doped polyarenes. This work also
serves as an illustration of how the recently developed iodine-
retentive coupling manifolds enabled by hypervalent iodine
serve as a versatile platform for downstream complexity buildup.
EXPERIMENTAL SECTION
■
General Comments. All reagents and solvents were from
commercial sources and used without further purification from freshly
opened containers. Anhydrous DMSO was supplied by Sigma-Aldrich
and used without additional purification. 1H NMR spectra were
recorded at 400 MHz, 13C NMR spectra were recorded at 100 MHz,
and 19F NMR spectra were recorded at 376 MHz. Chemical shifts are
reported in parts per million (ppm). H and 13C chemical shifts are
1
referenced relative to the residual solvent signal. High resolution mass
spectra were recorded on a maXis spectrometer and MicroTOF-Q,
both from Bruker Daltronics with electrospray ionization (ESI) in
positive mode and an Agilent 7200 Accurate Mass Q-TOF GC/MS
with electron impact ionization (EI). X-ray data were collected on a
BRUKER D8 VENTURE PHOTON 100 CMOS diffractometer with
Mo Kα radiation (λ = 0.71073 Å) using the φ and ω scans technique.
The structures were solved and refined by direct methods using the
SHELX.22 Data were corrected for absorption effects using the
multiscan method (SADABS). All non-hydrogen atoms were refined
anisotropically using SHELX.22 The coordinates of the hydrogen atoms
were calculated by mixed methods. Crystal data and experimental
details are given in the Supporting Information (Table S1).
Supplementary crystallographic data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via http://www.
ccdc.cam.ac.uk (2058419 and 2058420). All starting materials
(diaryliodonium salt and 1-aryl-5-iodoimidazoles) were prepared
according to slightly modified published procedures.17,23
a
Reaction conditions: iodonium salt 3 (0,25 mmol), S8 (0,125
mmol), Cs2CO3 (1 mmol) in DMSO (2.5 mL) at 100 °C for 4 h.
b
Amount of reagents was scaled down (see Experimental Section).
in drug and materials design.20 The approach, we envisioned,
would circumvent the use of metal-based catalysts20,21 and
appears to open an interesting path toward heteroatom-doped
polycyclic aromatics.
The reaction was tested under the previously published
conditions, which involve a DMSO medium and using elemental
sulfur as a radical source in the presence of Cs2CO3.12 Heating of
the reaction mixture led to the formation of a blue solution,
consistent with the formation of a trisulfide radical.12 The full
conversion of starting materials was achieved after 4 h, and with
the analysis of the reaction mixture confirming the formation of
the target poly-aromatic heterocyclic core 4. In general, the yield
Synthesis of Aryl Imidazolium Iodoacetates 1a−1q. Diary-
liodonium salts 1a−1n, 1p, 1q were prepared according to a slightly
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modified published procedure.17 All reactions were conducted in an argon
atmosphere.
(100 MHz, MeOD-d4) δ 179.8, 166.8, 142.1, 135.5, 134.7, 133.3, 129.8,
121.8, 104.2, 53.2, 23.9. HRMS (ESI) m/z: [M − OAc]+ Calcd for
C11H10IN2O2 328.9781; Found 328.9784.
General Procedure A (Described for 5 mmol Scale). A reaction
vessel was charged with NaIO4 (1.05 equiv, 5.25 mmol, 1.12 g), NaOAc
(2.2 equiv, 11 mmol, 0.902 g), and aryl iodide (for solid substrates).
The flask was evacuated and backfilled with argon (repeated 3 times).
Then a mixture of AcOH (7.5 mL) and Ac2O (0.75 mL) (and aryl
iodide if it is a liquid) was added through a reflux condenser. The
mixture was stirred at 115−125 °C on the oil bath for 4 h. It should be
noted that the full conversion of starting material was not achieved and
prolongation of reaction time did not lead to the better yield. After 4 h,
the reaction mass was cooled to room temperature, 30 mL of water was
added, and the aqueous layer was extracted with DCM 4 × 30 mL. The
combined organic layer was dried over anhydrous MgSO4, and the
solvent was removed under reduced pressure. The oily residue was re-
suspended in appropriate solvent (5 mL) and imidazole was added (10
mmol). The reaction mixture was stirred for 16−17 h at room
temperature in air. Then, the solvent was evaporated under reduced
pressure and the target product was isolated by precipitation with a
MeCN/Et2O mixture. The solid was filtered and washed with MeCN
(2 mL) and Et2O (3 × 10 mL).
General Procedure B (Described for 5 mmol Scale). A 50 mL
round-bottom flask equipped with a magnetic stir bar was charged with
NaIO4 (1.05 equiv, 5.25 mmol, 1.12 g), NaOAc (2.2 equiv, 11 mmol,
0.902 g), and aryl iodide (for solid substrates). The flask was evacuated
and backfilled with argon (repeated 3 times). Then a mixture of AcOH
(7.5 mL) and Ac2O (0.75 mL) (and aryl iodide if it is a liquid) was
added through a reflux condenser. This mixture was allowed to stir at
115−125 °C on the oil bath for 4 h. Usually full conversion of starting
material was not achieved. After 4 h, the reaction was cooled to room
temperature, 30 mL of water was added, and the aqueous layer was
extracted with DCM 4 × 30 mL. The combined organic layer was dried
over anhydrous MgSO4. The solvent was removed under reduced
pressure. Pentane was added to the residue, and the precipitate was
filtered and washed several times with pentane. Then solvent as
indicated has been added to the obtained solid, and the suspension was
allowed to stir for 5−10 min. Imidazole was added (neat, 2 equiv), and
the mixture was allowed to stir for 16−17 h at room temperature in the
air. Then the solvent was evaporated under reduced pressure and
MeCN was added. The mixture was allowed to stir until a precipitate
appeared and 1−2 h after that. The solid was filtered and washed with
MeCN (2 mL) and Et2O (3 × 10 mL) to obtain the desired product.
1a.
1c.
The reaction of 4-fluoroiodobenzene (5 mmol, 1.11 g) and NaIO4
(5.25 mmol, 1.12 g) according to general procedure B afforded
(diacetoxyiodo)arene as white crystals (1.425 g, 84%). The reaction of
(diacetoxyiodo)arene (3.82 mmol, 1.3 g) and imidazole (2 equiv, 7.64
mmol, 0.52 g) in MeOH (4 mL) afforded (4-fluorophenyl)(1H-
imidazol-5-yl)iodonium acetate 1c as a white solid, 957 mg, yield 72%.
mp = 118−122 °C.
1H NMR (400 MHz, DMSO-d6) δ 7.94−7.91 (m, 2H), 7.59 (d, J =
0.8 Hz, 1H), 7.43 (d, J = 0.4 Hz, 1H), 7.34−7.30 (m, 2H), 1.81 (s, 3H).
13C NMR (100 MHz, DMSO-d6) δ 172.9, 163.3 (d, J = 247 Hz), 145.3,
135.7 (d, J = 8 Hz), 133.0, 118.3 (d, J = 23 Hz), 112.2, 101.4, 22.6. 19
F
NMR (376 MHz, DMSO-d6) δ −110.2 to −109.0 (m). HRMS (ESI)
m/z: [M − OAc]+ Calcd for C9H7FIN2 288.9632; Found 288.9651.
1d.
The reaction of 4-chloroiodobenzene (5 mmol, 1.61 g) and imidazole
(10 mmol, 0.681 g) in MeOH according to general procedure A gave
(1H-imidazol-5-yl)(3-chlorophenyl)iodonium acetate 1d as a white
solid, 980 mg, yield 54%. mp = 135−137 °C.
1H NMR (400 MHz, MeOD-d4) δ 8.06−8.02 (m, 3H), 7.85 (d, J =
0.8 Hz, 1H), 7.54−7.50 (m, 2H), 1.89 (s, 3H). 13C NMR (100 MHz,
MeOD-d4) δ 180.2, 143.1, 139.7, 136.9, 132.9, 130.8, 114.9, 103.4, 24.2.
HRMS (ESI) m/z: [M − OAc]+ Calcd for C9H7ClIN2 304.9337;
Found 304.9328.
1e.
The reaction of 4-bromoiodobenzene (5 mmol, 1.42 g) and NaIO4
(5.25 mmol, 1.12 g) according to general procedure B afforded
(diacetoxyiodo)arene (1.263 g, 63%). The reaction of (diacetoxyiodo)-
arene (2.5 mmol, 1.003 g) and imidazole (2 equiv, 5 mmol, 0.34 g) in
MeOH (2.5 mL) afforded (4-bromophenyl)(1H-imidazol-5-yl)-
iodonium acetate 1e as a white solid, 940 mg, yield 92%. mp = 134−
136 °C.
The reaction of (diacetoxyiodo)benzene (5 mmol, 1.611 g) and
imidazole (10 mmol, 0.681 g) in MeOH according to general procedure
B afforded (1H-imidazol-5-yl)(phenyl)iodonium acetate 1a as a white
solid, 1.35 g, yield 82%.
1H NMR (400 MHz, MeOD-d4) δ 8.04 (d, J = 1.2 Hz, 1H), 7.98−
7.94 (m, 2H), 7.84 (d, J = 1.2 Hz, 1H), 7.69−7.65 (m, 2H), 1.89 (s,
3H). 13C NMR (100 MHz, MeOD-d4) δ 180.1, 142.2, 137.1, 135.9,
129.8, 128.0, 115.7, 104.2, 24.1. HRMS (ESI) m/z: [M − OAc]+ Calcd
for C9H7BrIN2 348.8832; Found 348.8822.
1H NMR (400 MHz, DMSO-d6) (the NMR spectra correspond with
the previously published17) δ 7.93−7.90 (m, 2H), 7.69 (d, J = 0.8 Hz,
1H), 7.56−7.52 (m, 1H), 7.50 (d, J = 0.8 Hz, 1H), 7.46−7.42 (m, 2H),
1.77 (s, 3H). 13C (100 MHz, DMSO-d6) δ 173.3, 144.8, 133.3, 132.6,
131.2, 130.8, 118.1, 101.6, 23.1.
1f.
1b.
The reaction of 4-iodotoluene (5 mmol, 1.09 g) and imidazole (10
mmol, 0.681 g) in MeOH according to general procedure A afforded
(1H-imidazol-5-yl)(4-methylphenyl)iodonium acetate 1f as a white
solid, 866 mg, yield 50%.
The reaction of methyl 4-iodobenzoate (5 mmol, 1.31 g) and imidazole
(10 mmol, 0.681 g) in MeOH according to general procedure A
afforded (1H-imidazol-5-yl)(4-(methoxycarbonyl)phenyl)iodonium
acetate 1b as a white solid, 892 mg, yield 46%. mp = 135−136 °C.
1H NMR (400 MHz, MeOD-d4) δ 8.18−8.14 (m, 2H), 8.09−8.06
(m, 3H), 7.85 (d, J = 1.2 Hz, 1H), 3.92 (s, 3H), 1.89 (s, 3H). 13C NMR
1H NMR (400 MHz, DMSO-d6) (the NMR spectra correspond to
the previously published17) δ 7.79 (d, J = 8.4 Hz, 2H), 7.67 (s, 1H),
7.50 (s, 1H), 7.25 (d, J = 8.0 Hz, 2H), 2.30 (s, 3H), 1.78 (s, 3H). 13C
NMR (100 MHz, DMSO-d6) δ 173.2, 144.6, 141.0, 133.3, 132.2, 131.7,
114.4, 101.8, 23.0, 20.7.
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1g.
1k.
The reaction of 2-iodotoluene (5 mmol, 1.09 g) and imidazole (10
mmol, 0.681 g) in MeOH according to general procedure A afforded
(1H-imidazol-5-yl)(2-methylphenyl)iodonium acetate 1k as a white
solid, 985 mg, yield 57%.
The reaction of 3-bromoiodobenzene (5 mmol, 1,42 g) and NaIO4
(5.25 mmol, 1.12 g) according to general procedure B afforded
(diacetoxyiodo)arene (1.335 g, 67%). The reaction of (diacetoxyiodo)-
arene (2.5 mmol, 1.003 g) and imidazole (2 equiv, 5 mmol, 0.34 g) in
MeOH (2.5 mL) afforded (3-bromophenyl)(1H-imidazol-5-yl)-
iodonium acetate 1g as a white solid, 736 mg, yield 72%.
1H NMR (400 MHz, MeOD-d4) (the NMR spectra correspond with
the previously published17) δ 8.29 (s, 1H), 8.05−8.03 (m, 2H), 7.85(s,
1H), 7.81 (d, J = 8.0 Hz, 1H), 7.42 (t, J = 8.0 Hz, 1H), 1.89 (s, 3H). 13C
NMR (100 MHz, MeOD-d4) δ 179.9, 142.1, 137.6, 136.4, 134.2, 134.1,
129.7, 125.1, 117.6, 104.5, 23.9.
1H NMR (400 MHz, MeOD-d4) (the NMR spectra correspond with
the previously published17) δ 8.21 (d, J = 8.0 Hz, 1H), 8.02 (d, J = 0.4
Hz, 1H), 7.81 (d, J = 0.4 Hz, 1H), 7.58−7.53 (m, 2H), 7.29−7.25 (m,
1H), 2.73 (s, 3H), 1.88 (s, 3H). 13C NMR (100 MHz, MeOD-d4) δ
180.0, 142.1, 141.4, 138.0, 134.2, 132.7, 130.4, 128.7, 122.4, 104.0, 25.5,
24.0.
1l.
1h.
The reaction of 2-fluoroiodobenzene (5 mmol, 1.11 g) and NaIO4
(5.25 mmol, 1.12 g) according to general procedure B afforded
(diacetoxyiodo)arene (0.903 g, 53%). The reaction of (diacetoxyiodo)-
arene (2.4 mmol, 822 mg) and imidazole (2 equiv, 4.8 mmol, 0.326 g)
in MeOH (2.5 mL) afforded (2-fluorophenyl)(1H-imidazol-5-yl)-
iodonium acetate 1l as a white solid, 652 mg, yield 78%. mp = 152−152
°C.
The reaction of 3-iodotoluene (5 mmol, 1.09 g) and imidazole (10
mmol, 0.681 g) in MeOH according to general procedure A afforded
(1H-imidazol-5-yl)(3-methylphenyl)iodonium acetate 1h as a white
solid, 807 mg, yield 47%. mp = 145−146 °C.
1H NMR (400 MHz, MeOD-d4) δ 8.03 (d, J = 1.2 Hz, 1H), 7.92 (s,
1H), 7.86−7.84 (m, 2H), 7.47 (d, J = 7.6 Hz, 1H), 7.37 (t, J = 8.0 Hz,
1H), 2.39 (s, 3H), 1.89 (s, 3H). 13C NMR (100 MHz, MeOD-d4) δ
180.0, 143.8, 141.6, 135.7, 134.0, 132.5, 132.5, 129.1, 117.2, 104.3, 24.0,
21.3. HRMS (ESI) m/z: [M − OAc]+ Calcd for C10H10IN2 284.9883,
found: 284.9866.
1H NMR (400 MHz, DMSO-d6) δ 8.10 (ddd, J = 7.6, 6.0, 1.6 Hz,
1H), 7.64 (d, J = 0.8 Hz, 1H), 7.63−7.57 (m, 1H), 7.45 (td, J = 8.0, 1.2
Hz, 2H), 7.24 (td, J = 7.6, 1.2 Hz, 1H), 1,74 (s, 3H). 13C NMR (100
MHz, DMSO-d6) δ 173.5, 159.3 (d, J = 246 Hz), 143.3, 136.6, 134.1 (d,
J = 7 Hz), 130.8, 126.9 (d, J = 3 Hz), 116.3 (d, J = 23 Hz), 106.9 (d, J =
24 Hz), 103.9, 23.1. 19F NMR (376 MHz, DMSO-d6) δ −99.1 to −99.0
(m). HRMS (ESI) m/z: [M − OAc]+ Calcd for C9H7FIN2 288.9632;
Found 288.9640.
1i.
1m.
The reaction of 3-methoxyiodobenzene (5 mmol, 1.17 g) and imidazole
(10 mmol, 0.681 g) in MeOH according to general procedure A
afforded (1H-imidazol-5-yl)(3-methoxyphenyl)iodonium acetate 1i as
a white solid, 828 mg, yield 46%.
The reaction of (diacetoxyiodo)benzene (5 mmol, 1.61 g) and 2-
methylimidazole (10 mmol, 0.82 g) in MeOH according to general
procedure B afforded (2-methyl-1H-imidazol-5-yl)(phenyl)iodonium
acetate 1m as a white solid, 999 mg, yield 58%.
1H NMR (400 MHz, DMSO-d6) (the NMR spectra correspond with
the previously published17) δ 7.70 (d, J = 0.8 Hz, 1H), 7.54−7.52 (m,
2H), 7.43 (ddd, J = 8.0, 1.6, 0.8 Hz, 1H), 7.35 (t, J = 8.0 Hz, 1H), 7.10
(ddd, J = 8.4, 2.4, 0.8 Hz, 1H), 3.75 (s, 3H), 1.77 (s, 3H). 13C NMR
(100 MHz, DMSO-d6) δ 173.3, 160.2, 144.7, 132.7, 131.8, 125.1, 118.8,
118.2, 116.5, 101.6, 55.7, 23.1.
1H NMR (400 MHz, MeOD-d4) (the NMR spectra correspond with
the previously published17) δ 8.08−8.05 (m, 2H), 7.93 (s, 1H), 7.68−
7.63 (m, 1H), 7.54−7.48 (m, 2H), 2.42 (s, 3H), 1.89 (s, 3H). 13C NMR
(100 MHz, MeOD-d4) δ 180.1, 140.8, 138.5, 135.3, 133.2, 132.9, 117.2,
104.3, 24.1, 10.8.
1n.
1j.
The reaction of 2-methoxyiodobenzene (5 mmol, 1,17 g) and NaIO4
(5.25 mmol, 1.12 g) according to general procedure B afforded
(diacetoxyiodo)arene (1,128 g, 64%). The reaction of (diacetoxyiodo)-
arene (3,16 mmol, 1,111 mg) and 4-methylimidazole (2 equiv, 6.32
mmol, 0.518 g) in MeOH (3 mL) afforded (4-methoxyphenyl)(4-
methyl-1H-imidazol-5-yl)iodonium acetate 1n as a white solid, 447 mg,
yield 38%. mp = 134−135 °C.
The reaction of 2-bromoiodobenzene (5 mmol, 1,415 g) and NaIO4
(5.25 mmol, 1.12 g) according to general procedure B afforded
(diacetoxyiodo)arene (1.051 g, 52%). The reaction of (diacetoxyiodo)-
arene (2.52 mmol, 1.011 mg) and imidazole (2 equiv, 5.04 mmol, 0.343
g) in MeOH (2,5 mL) afforded (2-bromophenyl)(1H-imidazol-5-
yl)iodonium acetate 1j as a white solid, 742 mg, yield 72%.
1H NMR (400 MHz, MeOD-d4) (the NMR spectra correspond with
the previously published17) δ 8.26 (dd, J = 8.0, 1.6 Hz, 1H), 8.07 (d, J =
0.8 Hz, 1H), 7.91 (dd, J = 8.0, 1.6 Hz, 1H), 7.83 (d, J = 1.2 Hz, 1H), 7.56
(td, J = 7.6, 1.6 Hz, 1H), 7.46 (td, J = 7.6, 1.6 Hz, 1H), 1.89 (s, 3H). 13C
NMR (100 MHz, MeOD-d4) δ 179.9, 141.7, 139.4, 135.4, 134.9, 131.5,
129.5, 127.8, 123.2, 105.1, 23.9.
1H NMR (400 MHz, MeOD-d4) δ 7.96 (d, J = 9.2 Hz, 2H), 7.77 (s,
1H), 7.03 (d, J = 9.2 Hz, 2H), 3.83 (s, 3H), 2.49 (s, 3H), 1.88 (s, 3H).
13C NMR (100 MHz, MeOD-d4) δ 180.0, 164.2, 140.4, 137.7, 137.5,
118.5, 105.9, 105.0, 56.3, 24.1, 10.8. HRMS (ESI) m/z: [M − OAc]+
Calcd for C11H12IN2O 314.9989; Found 314.9989.
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1p.
removed by rotary evaporator under reduced pressure, and 1-aryl-5-
iodoimidazole was isolated by column chromatography (hexane:EtOAc
(10:1 → 3:2).
2a.
The reaction of 3,5-dimethyliodobenzene (5 mmol, 1.16 g) and
imidazole (10 mmol, 0.681 g) in MeOH according to general procedure
A afforded (1H-imidazol-5-yl)(3,5-dimethylphenyl)iodonium acetate
1p as a white solid, 1.026 g, yield 57%. mp = 135−136 °C.
1H NMR (400 MHz, MeOD-d4) δ 8.02 (d, J = 0.8 Hz, 1H), 7.83 (d, J
= 0.8 Hz, 1H), 7.70 (s, 2H), 7.29 (s, 1H), 2.34 (s, 6H), 1.89 (s, 3H). 13C
NMR (100 MHz, MeOD-d4) δ 180.1, 143.4, 141.7, 134.8, 132.8, 129.2,
117.0, 104.0, 24.1, 21.2. HRMS (ESI) m/z: [M − OAc]+ Calcd for
C11H12IN2 299.0040; Found 299.0040.
The reaction of acetate 1a (2 mmol, 0.66 g) in HFIP solution according
to the general procedure after column chromatography (hexane:EtOAc
(10:1 → 3:2)) afforded 1-phenyl-5-iodoimidazole 2a as off-white solid,
0.352 g, yield: 65%.
1H NMR (400 MHz, DMSO-d6) (the NMR spectra correspond with
the previously published17) δ 8.05 (s, 1H), 7.59−7.51 (m, 3H), 7.44−
7.42 (m, 2H), 7.19 (s, 1H). 13C NMR (100 MHz, DMSO-d6) δ 140.5,
136.9, 136.7, 129.4, 128.9, 126.7, 74.1.
1q.
2b.
The reaction of (diacetoxyiodo)benzene (5 mmol, 1.61 g) and 4-
methylimidazole (10 mmol, 0,82 g) in MeOH according to general
procedure B afforded (1H-4-methylimidazol-5-yl)(phenyl)iodonium
acetate 1q as a white solid, 1.007 g, yield 59%.
The reaction of acetate 1b (2 mmol, 0.776 g) in HFIP solution
according to the general procedure after column chromatography
(hexane:EtOAc (10:1 → 3:2)) afforded methyl 4-(5-iodoimidazol-1-
yl)benzoate 2b as a white solid, 0.459 g, yield: 70%. mp = 125−127 °C.
1H NMR (400 MHz, DMSO-d6) δ 8.14−8.12 (m, 3H), 7.63 (d, J =
7.6 Hz, 2H), 7.24 (s, 1H), 3.90 (s, 3H). 13C NMR (100 MHz, DMSO-
d6) δ 165.5, 140.6, 140.4, 137.6, 130.3, 129.7, 126.8, 73.4, 52.5. HRMS
(EI) m/z: [M]+· Calcd for C11H9IN2O2 327.9703; Found 327.9703.
2c.
1H NMR (400 MHz, MeOD-d4) (the NMR spectra correspond with
the previously published17) δ 8.05−8.02 (m, 2H), 7.79 (s, 1H), 7.67−
7.63 (m, 1H), 7.53−7.48 (m, 2H), 2.50 (s, 3H), 1.89 (s, 3H). 13C NMR
(100 MHz, MeOD-d4) δ 180.1, 151.4, 135.5, 133.2, 132.9, 128.9, 117.4,
103.0, 24.1, 13.7.
Synthesis of (3,5-Dichlorophenyl)(1H-imidazol-5-yl)-
iodonium Acetate 1o.23 1o.
The reaction of acetate 1c (2 mmol, 0.696 g) in HFIP solution
according to the general procedure after column chromatography
(hexane:EtOAc (10:1 → 3:2)) afforded 1-(4-fluorophenyl)-5-
iodoimidazole 2c as a white solid, 0.271 g, yield: 47%. mp = 93−95 °C.
1H NMR (400 MHz, MeOD-d4) δ 7.99 (d, J = 0.8 Hz, 1H), 7.46−
7.43 (m, 2H), 7.33−7.29 (m, 2H), 7.20 (d, J = 0.8 Hz, 1H). 13C NMR
(100 MHz, MeOD-d4) δ 164.3 (d, J = 249.5 Hz), 141.6, 137.6, 134.3(d,
J = 3 Hz), 130.3(d, J = 9.1 Hz), 117.3 (d, J = 24.2 Hz), 74.2. 19F NMR
(376 MHz, MeOD-d4) δ −113.7 to −113.6 (m). HRMS (EI) m/z:
[M]+· Calcd for C9H6FIN2287.9554; Found 287.9553.
3,5-Dichloroiodobenzene (2 mmol, 0.546 g) was dissolved in a mixture
of AcOH (18 mL) and TfOH (12 mmol, 1.1 mL), followed by
portionwise addition of Na3BO3·4H2O (20 mmol, 3.077 g) over 30 min
under an argon atmosphere. The flask was capped, and the mixture was
heated on the oil bath to 50 °C during 6 h. Then 40 mL of water was
added. The water layer was extracted with DCM (4 × 25 mL). The
combined organic layer was dried over MgSO4, and the solvent was
evaporated. The 3,5-dichloro(diacetoxyiodo)benzene (57%, 1.14
mmol, 0.445 g) was precipitated by addition of pentane. The prepared
3,5-dichloro(diacetoxyiodo)benzene was dissolved in MeOH (1.5
mL), and imidazole (2.3 mmol, 0.156 g) was added. The mixture was
stirred for 16 h, and the solvent was removed in vacuo. MeCN (2 mL)
was added to the oily residue, and the precipitated solid was filtered and
washed with Et2O several times to give (3,5-dichlorophenyl)(1H-
imidazol-5-yl)iodonium acetate 1o as a white solid, 355 mg, yield 78%.
mp = 140−142 °C.
2d.
The reaction of acetate 1d (2 mmol, 0.729 g) in HFIP solution
according to the general procedure after column chromatography
(hexane:EtOAc (10:1 → 3:2)) afforded 1-(4-chlorophenyl)-5-
iodoimidazole 2d as an off-white solid, 0.377 g, yield: 62%.
1H NMR (400 MHz, DMSO-d6) (the NMR spectra correspond with
the previously published17) δ 8.06 (d, J = 0.4 Hz, 1H), 7.65 (d, J = 8.4
Hz, 2H), 7.48 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 0.4 Hz, 1H). 13C NMR
(100 MHz, DMSO-d6) δ 140.6, 137.1, 135.5, 133.6, 129.4, 128.6, 74.1.
2e.
1H NMR (400 MHz, MeOD-d4) δ 8.11 (d, J = 1.6 Hz, 2H), 8.06 (s,
1H), 7.87 (s, 1H), 7.75 (t, J = 1.6 Hz, 1H), 1.89 (s, 3H). 13C NMR (100
MHz, MeOD-d4) δ 179.9, 142.0, 138.0, 133.5, 133.3, 129.7, 117.8,
105.3, 23.9. HRMS (ESI) m/z: [M − OAc]+ Calcd for C9H6Cl2IN2
338.8947; Found 338.8931.
Synthesis of 1-Aryl-5-Iodoimidazoles 2a−2q. General Pro-
cedure (Described for 2 mmol Scale). 1-Aryl-5-iodoimidazoles 2a−
2q were prepared according to a published procedure17
Cu(OTf)2 (5 mol %, 0.1 mmol, 0.036 g), Cs2CO3 (1.5 equiv, 3
mmol, 0.978 g), and N-methylbenzimidazole (if not stated otherwise)
(20 mol %, 0.4 mmol, 0.053 g) were charged in a 50 mL round-bottom
flask equipped with a magnetic stir bar. 10 mL of 1,1,1,3,3,3-
hexafluoropropan-2-ol (HFIP) had been added, and the mixture was
allowed to stir for 30 min. Then aryl(imidazolyl)iodonium acetate 1 (2
mmol) was added (neat), the flask was capped, and reaction mass was
heated to 50 °C on the oil bath for 16 h. After that, the solvent was
The reaction of acetate 1e (2 mmol, 0.818 g) in HFIP solution
according to the general procedure after column chromatography
(hexane:EtOAc (10:1 → 3:2)) afforded 1-(4-bromophenyl)-5-
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iodoimidazole 2e as a pale brown solid, 0.401 g, yield: 58%. mp = 119−
2j.
120 °C.
1H NMR (400 MHz, MeOD-d4) δ 8.01 (d, J = 1.2 Hz, 1H), 7.75−
7.72 (m, 2H), 7.37−7.35 (m, 2H), 7.21 (d, J = 0.8 Hz, 1H). 13C NMR
(100 MHz, MeOD-d4) δ 141.5, 137.9, 137.3, 133.8, 129.9, 124.4, 73.6.
HRMS (ESI) m/z: [M + H]+ Calcd for C9H7BrIN2 348.8832; Found
348.8860.
The reaction of acetate 1j (2 mmol, 0.818 g) in HFIP solution
according to the general procedure after column chromatography
(hexane:EtOAc (10:1 → 3:2)) afforded 1-(2-bromophenyl)-5-
iodoimidazole 2j as a white solid, 0.420 g, yield: 60%.
2f.
1H NMR (400 MHz, MeOD-d4) (the NMR spectra correspond with
the previously published17) δ 7.95 (d, J = 1.2 Hz, 1H), 7.83 (dd, J = 8.0,
1.2 Hz, 1H), 7.57 (td, J = 7.6, 1.6 Hz, 1H), 7.53−7.48 (m, 1H), 7.44
(dd, J = 7.6, 1.6 Hz, 1H), 7.22 (d, J = 1.2 Hz, 1H). 13C NMR (100 MHz,
MeOD-d4) δ 141.6, 137.5, 137.0, 134.7, 132.9, 131.6, 129.8, 123.9, 74.9.
2k.
The reaction of acetate 1f (2 mmol, 0.688 g) in HFIP solution
according to the general procedure after column chromatography
(hexane:EtOAc (10:1 → 3:2)) afforded 1-(4-methylphenyl)-5-
iodoimidazole 2f as an off-white solid, 0.392 g, yield: 69%.
1H NMR (400 MHz, DMSO-d6) (the NMR spectra correspond with
the previously published17) δ 8.00 (d, J = 0.8 Hz, 1H), 7.36 (d, J = 8.4
Hz, 2H), 7.29 (d, J = 8.4 Hz, 2H), 7.17 (d, J = 0.8 Hz, 1H), 2.39 (s, 3H).
13C NMR (100 MHz, DMSO-d6) δ 140.5, 138.6, 136.8, 134.2, 129.8,
126.5, 74.3, 20.7.
The reaction of acetate 1k (2 mmol, 0.688 g) in HFIP solution
according to the general procedure after column chromatography
(hexane:EtOAc (10:1 → 3:2)) afforded 1-(2-methylphenyl)-5-
iodoimidazole 2k as a pale yellow oil, 0.318 g, yield: 56%.
1H NMR (400 MHz, DMSO-d6) (the NMR spectra correspond with
the previously published17) δ 7.96 (d, J = 0.8 Hz, 1H), 7.49−7.44 (m,
2H), 7.40−7.36 (m, 1H), 7.24 (d, J = 7.2 Hz, 1H), 7.21 (d, J = 0.8 Hz,
1H), 1.95 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 140.5, 136.1,
136.1, 135.6, 130.9, 129.8, 128.5, 127.0, 75.2, 17.2.
2g.
The reaction of acetate 1g (2 mmol, 0.818 g) in HFIP solution
according to the general procedure after column chromatography
(hexane:EtOAc (10:1 → 3:2)) afforded 1-(3-bromophenyl)-5-
iodoimidazole 2g as an off-white solid, 0.377 g, yield: 54%.
1H NMR (400 MHz, DMSO-d6) (the NMR spectra correspond with
the previously published17) δ 8.10 (s, 1H), 7.76−7.73 (m, 2H), 7.55−
7.47 (m, 2H), 7.20 (s, 1H). 13C NMR (100 MHz, DMSO-d6) δ 140.7,
138.0, 137.1, 131.8, 131.2, 129.4, 126.0, 121.8, 74.0.
2l.
The reaction of acetate 1l (2 mmol, 0.696 g) in HFIP solution
according to the general procedure after column chromatography
(hexane:EtOAc (10:1 → 3:2)) afforded 1-(2-fluorophenyl)-5-
iodoimidazole 2l as a white solid, 0.288 g, yield: 50%. mp = 60−62 °C.
1H NMR (400 MHz, MeOD-d4) δ 7.99 (s, 1H), 7.64−7.58 (m, 1H),
7.45−7.36 (m, 3H), 7.23 (s, 1H). 13C NMR (100 MHz, MeOD-d4) δ
158.7 (d, J = 250 Hz), 142.2, 137.4, 133.1 (d, J = 8 Hz), 131.0, 126.2 (d,
J = 4 Hz), 125.9 (d, J = 13 Hz), 117.8 (d, J = 20 Hz), 74.8. 19F NMR
(376 MHz, MeOD-d4) δ −123.2 to −123.1 (m). HRMS (EI) m/z:
[M]+· Calcd for C9H6FIN2 287.9554; Found 287.9554.
2h.
The reaction of acetate 1h (2 mmol, 0.688 g) in HFIP solution
according to the general procedure after column chromatography
(hexane:EtOAc (10:1 → 3:2)) afforded 1-(3-methylphenyl)-5-
iodoimidazole 2h as an off-white solid, 0.426 g, yield: 75%. mp =
61−62 °C.
2m.
1H NMR (400 MHz, MeOD-d4) δ 7.95 (s, 1H), 7.43 (t, J = 7.6 Hz,
1H), 7.36 (d, J = 7.6 Hz, 1H), 7.22 (s, 1H), 7.19−7.17 (m, 2H), 2.44 (s,
3H). 13C NMR (100 MHz, MeOD-d4) δ 141.4, 141.1, 138.0, 137.6,
131.2, 130.3, 128.5, 125.0, 73.7, 21.2. HRMS (ESI) m/z: [M + H]+
Calcd for C10H10IN2 284.9883; Found 284.9874.
The reaction of acetate 1m (2 mmol, 0.688 g) in HFIP solution
according to the general procedure after column chromatography
(hexane:EtOAc (10:1 → 3:2)) afforded 1-phenyl-2-methyl-5-iodoimi-
dazole 2m as an off-white solid, 0.230 g, yield: 40%.
2i.
1H NMR (400 MHz, DMSO-d6) (the NMR spectra correspond with
the previously published17) δ 7.60−7.52 (m, 3H), 7.34−7.32 (m, 2H),
7.04 (s, 1H), 2.19 (s, 1H). 13C NMR (100 MHz, DMSO-d6) δ 147.2,
137.1, 134.4, 129.5, 129.3, 128.2, 73.5, 14.5.
2n.
The reaction of acetate 1i (2 mmol, 0.72 g) in HFIP solution according
to the general procedure after column chromatography (hexane:EtOAc
(10:1 → 3:2)) afforded 1-(3-methoxyphenyl)-5-iodoimidazole 2i as an
off-white solid, 0.452 g, yield: 75%.
1H NMR (400 MHz, DMSO-d6) (the NMR spectra correspond with
the previously published17) δ 8.04 (s, 1H), 7.47 (t, J = 8.0 Hz, 1H), 7.18
(s, 1H), 7.10 (dd, J = 8.4, 2.4 Hz, 1H), 7.01−6.98 (m, 2H), 3.82 (s, 3H).
13C NMR (100 MHz, DMSO-d6) δ 159.7, 140.5, 137.6, 136.9, 130.2,
118.6, 114.6, 112.3, 73.8, 55.5.
The reaction of acetate 1n (2 mmol, 0.748 g) in HFIP solution
according to the general procedure after column chromatography
(hexane:EtOAc (10:1 → 3:2)) afforded 1-(4-methoxyphenyl)-4-
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methyl-5-iodoimidazole 2n as a yellowish solid, 0.289 g, yield: 46%. mp
= 83−85 °C.
resulting suspension was allowed to stir for 1 h at room temperature.
The final solid was filtered and washed with cold water (2 × 3 mL),
Et2O (3 × 5 mL) and dried under vacuum.
3a.
1H NMR (400 MHz, DMSO-d6) δ 7.93 (s, 1H), 7.32−7.28 (m, 2H),
7.10−7.06 (m, 2H), 3.82 (s, 3H), 2.16 (s, 3H). 13C NMR (100 MHz,
DMSO-d6) δ 159.3, 142.2, 140.1, 130.1, 128.1, 114.4, 74.3, 55.6, 14.6.
HRMS (EI) m/z: [M]+· Calcd for C11H11IN2O 313.9911; Found
313.9911.
2o.
The reaction of 1-phenyl-5-iodoimidazole 2a (0.5 mmol, 135 mg) with
one portion of Oxone in H2SO4 according to the general procedure
afforded benzo[d]imidazo[5,1-b][1,3]iodazol-4-ium hydrogen sulfate
3a as a white solid, 154 mg, yield: 84%. mp = 201−203 °C.
1H NMR (400 MHz, DMSO-d6) δ 9.19 (s, 1H), 8.33 (d, J = 7.6 Hz,
1H), 8.13 (d, J = 8.0 Hz, 1H), 7.81 (t, J = 7.6 Hz, 1H), 7.53 (t, J = 7.6
Hz, 1H), 7.41 (s, 1H). 13C NMR (100 MHz, DMSO-d6) δ 135.7, 134.8,
131.9, 131.50, 131.3, 128.6, 117.3, 112.2, 97.9. HRMS (ESI) m/z: [M −
HSO4]+ Calcd for C9H6IN2 268.9570; Found 268.9580.
3b.
The reaction of acetate 1o (0.875 mmol, 0.349 g) in HFIP solution
according to the general procedure after column chromatography
(hexane:EtOAc (10:1 → 3:2)) afforded 1-(3,5-dichlorophenyl)-5-
iodoimidazole 2o as an off-white solid, 0.171 g, yield: 58%. mp = 127−
131 °C.
1H NMR (400 MHz, MeOD-d4) δ 8.06 (d, J = 0.8 Hz, 1H), 7.69−
7.68 (m, 1H), 7.51 (d, J = 2 Hz, 2H), 7.23 (d, J = 0.8 Hz, 1H). 13C NMR
(100 MHz, MeOD-d4) δ 141.7, 140.0, 138.3, 136.8, 130.5, 127.1, 73.3.
HRMS (ESI) m/z: [M + H]+ Calcd for C9H6Cl2IN2 338.8947; Found
338.8966.
2p.
The reaction of methyl 4-(5-iodo-imidazol-1-yl)benzoate 2b (0.5
mmol, 164 mg) with an additional portion of Oxone (0.2 and 0.3 g,
respectively, for the first and the second batch of the oxidant) in H2SO4 (0.8
mL for both portions) according to the general procedure afforded 6-
(methoxycarbonyl)benzo[d]imidazo[5,1-b][1,3]iodazol-4-ium hydro-
gen sulfate 3b as an off-white solid, 212 mg, yield: 81%. mp = 248−249
°C.
The reaction of acetate 1p (2 mmol, 0.716 g) in HFIP solution
according to the general procedure after column chromatography
(hexane:EtOAc (10:1 → 3:2)) afforded 1-(3,5-dimethylphenyl)-5-
iodoimidazole 2p as an off-white solid, 0.375 g, yield: 63%. mp = 132−
134 °C.
1H NMR (400 MHz, DMSO-d6) δ 9.28 (s, 1H), 8.67 (d, J = 1.6 Hz,
1H), 8.43 (d, J = 8.4 Hz, 1H), 8.35 (dd, J = 8.4, 2 Hz, 1H), 7.45 (s, 1H),
3.92 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 164.4, 138.3, 136.4,
132.9, 132.3, 131.9, 129.1, 117.2, 113.1, 98.9, 52.9. HRMS (ESI) m/z:
[M − HSO4]+ Calcd for C11H8IN2O2 326.9625; Found 326.9625.
3c.
1H NMR (400 MHz, DMSO-d6) δ 7.99 (s, 1H), 7.17 (s, 2H), 7.03 (s,
2H), 2.35 (s, 6H). 13C NMR (100 MHz, DMSO-d6) δ 140.4, 138.8,
136.8, 136.5, 130.2, 124.2, 74.0, 20.7. HRMS (EI) m/z: [M]+· Calcd for
C11H11IN2 297.9961; Found 297.9961.
2q.
The reaction of 1-(4-fluorophenyl)-5-iodoimidazole 2c (0.5 mmol, 144
mg) with an additional portion of Oxone in H2SO4 according to the
general procedure afforded 6-fluorobenzo[d]imidazo[5,1-b][1,3]-
iodazol-4-ium hydrogen sulfate 3c as an off-white solid, 115 mg,
yield: 60%. mp = 224−227 °C.
The reaction of acetate 1q (2 mmol, 0.688 g) in HFIP solution
according to the general procedure after column chromatography
(hexane:EtOAc (10:1 → 3:2)) afforded 4-methyl-1-phenyl-5-iodoimi-
dazole 2q as an off-white solid, 0.484 g, yield: 87%.
1H NMR (400 MHz, MeOD-d4) (the NMR spectra correspond with
the previously published17) δ 7.95 (s, 1H), 7.58−7.53 (m, 3H), 7.39−
7.37 (m, 2H), 2.27 (s, 3H). 13C NMR (100 MHz, MeOD-d4) δ 144.0,
140.9, 138.6, 130.5, 130.4, 128.0, 73.0, 14.4.
1H NMR (400 MHz, DMSO-d6) δ 9.16 (s, 1H), 8.38 (dd, J = 9.2, 4.4
Hz, 1H), 7.91 (dd, J = 7.6, 2,8 Hz, 1H), 7.78 (td, J = 8.8, 2.8 Hz, 1H),
7.41 (s, 1H). 13C NMR (100 MHz, DMSO-d6) δ 159.9 (d, J = 247 Hz),
135.7, 132.1 (d, J = 2 Hz), 131.6, 119.4 (d, J = 24 Hz), 118.3 (d, J = 18
Hz), 118.1, 113.1 (d, J = 10 Hz), 98.6. 19F NMR (376 MHz, DMSO-d6)
δ 111.8−111.7 (m). HRMS (ESI) m/z: [M − HSO4]+ Calcd for
C9H5FIN2 286.9476; Found 286.9462.
Synthesis of Cyclic Iodonium Salts 3a−3q. General Procedure.
A 10 mL reaction tube equipped with a stir bar was charged with 96%
H2SO4 (0.8 mL) and cooled to between 0 and 5 °C. Then, finely ground
1-aryl-5-iodoimidazole 2 (0.5 mmol) was added, and the resulting
mixture was stirred for 20 min, followed by the addition of finely ground
Oxone (1.3 equiv, 0.325 mmol, 0.2 g) in one portion. The stirring was
continued for 1 h between 0 and 5 °C. Next, the ice−water bath was
removed and stirring was continued for 1 h at room temperature. For
some substrates, an additional portion of Oxone (0.325 mmol, 0.2 g)
and H2SO4 (0.8 mL) was required after 2 h of reaction (addition under
cooling with ice−water bath). After full consumption of the initial
material, as gauged by TLC (hexane:EtOAc = 2:1), ice was added to the
reaction mixture (1−2 g). Then, the mixture was diluted with cold
water to the total volume of 7 mL. A 9 M NaOH solution was added
dropwise with cooling by ice−water bath until the appearance of the
precipitate (approximately 2−2.5 mL for 0.8 mL of H2SO4); the
3d.
The reaction of 1-(4-chlorophenyl)-5-iodoimidazole 2d (0.5 mmol,
153 mg) with an additional portion of Oxone in H2SO4 according to the
general procedure afforded 6-chlorobenzo[d]imidazo[5,1-b][1,3]-
iodazol-4-ium hydrogen sulfate 3d as an off-white solid, 140 mg,
yield: 70%. mp = 243−245 °C.
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1H NMR (400 MHz, DMSO-d6) δ 9.06 (s, 1H), 8.38 (s, 1H), 8.24
(d, J = 8.8 Hz, 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.32 (s, 1H). 13C NMR
(100 MHz, DMSO-d6) δ 135.9, 134.3, 132.0, 131.6, 131.5, 130.4, 118.2,
113.5, 98.6. HRMS (ESI) m/z: [M − HSO4]+ Calcd for C9H5ClIN2
302.9180; Found 302.9165.
1H NMR (400 MHz, DMSO-d6) δ 9.10 (s, 1H), 8.18 (d, J = 0.8 Hz,
1H), 8.05 (d, J = 8.4 Hz, 1H), 7.37 (s, 1H), 7.2−7.30 (m, 1H), 2.47 (s,
3H). 13C NMR (100 MHz, DMSO-d6) δ 142.3, 135.3, 134.8, 131.5,
131.1, 129.2, 117.4, 108.8, 99.0, 20.8. HRMS (ESI) m/z: [M − HSO4]+
Calcd for C10H8IN2 282.9727; Found 282.9726.
3i.
3e.
The reaction of 1-(4-bromophenyl)-5-iodoimidazole 2e (0.5 mmol,
175 mg) with an additional portion of Oxone in H2SO4 according to the
general procedure afforded 6-bromobenzo[d]imidazo[5,1-b][1,3]-
iodazol-4-ium hydrogen sulfate 3e as a pale brown solid, 180 mg,
yield: 81%. mp = 255−258 °C.
The reaction of 1-(3-methoxyphenyl)-5-iodoimidazole 2i (0.5 mmol,
150 mg) with one portion of Oxone in H2SO4 according to the general
procedure afforded 7-methoxybenzo[d]imidazo[5,1-b][1,3]iodazol-4-
ium hydrogen sulfate 3i as an off-white solid, 150 mg, yield: 76%. mp =
251−253 °C.
1H NMR (400 MHz, DMSO-d6) δ 9.20 (s, 1H), 8.29 (d, J = 8.4 Hz,
1H), 8.20 (d, J = 2,0 Hz, 1H), 8.06 (dd, J = 8.8, 2.0 Hz, 1H), 7.41 (s,
1H). 13C NMR (100 MHz, DMSO-d6) δ 136.0, 134.8, 134.6, 133.1,
131.6, 119.4, 118.7, 113.8, 98.5. HRMS (ESI) m/z: [M − HSO4]+
Calcd for C9H5BrIN2 346.8675; Found 346.8701.
1H NMR (400 MHz, DMSO-d6) δ 9.19 (s, 1H), 7.98 (d, J = 2.8 Hz,
1H), 7.96 (d, J = 9.2 Hz, 1H), 7.38 (s, 1H), 7.12 (dd, J = 9.2, 2.8 Hz,
1H), 3.91 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 162.4, 135.9,
135.7, 131.8, 131.6, 115.2, 102.9, 100.8, 98.1, 56.4. HRMS (ESI) m/z:
[M − HSO4]+ Calcd for C10H8IN2O 298.9676; Found 298.9665.
3j.
3f.
The reaction of 1-(4-methylphenyl)-5-iodoimidazole 2f (0.5 mmol,
142 mg) with one portion of Oxone in H2SO4 according to the general
procedure afforded 6-methylbenzo[d]imidazo[5,1-b][1,3]iodazol-4-
ium hydrogen sulfate 3f as an off-white solid, 173 mg, yield: 91%. mp
= 231−233 °C.
The reaction of 1-(2-bromophenyl)-5-iodoimidazole 2j (0.5 mmol, 175
mg) with an additional portion of Oxone in H2SO4 according to the
general procedure afforded 8-bromobenzo[d]imidazo[5,1-b][1,3]-
iodazol-4-ium hydrogen sulfate 3j as an off-white solid, 125 mg,
yield: 56%. mp = 179−181 °C.
1H NMR (400 MHz, DMSO-d6) δ 9.14 (s, 1H), 8.21 (d, J = 8.0 Hz,
1H), 7.89 (s, 1H), 7.62 (d, J = 8.4 Hz, 1H), 7.39 (s, 1H), 2.44 (s, 3H).
13C NMR (100 MHz, DMSO-d6) δ 138.7, 135.4, 132.6, 132.5, 131.4,
130.8, 116.8, 112.0, 97.6, 20.8. HRMS (ESI) m/z: [M − HSO4]+ Calcd
for C10H8IN2 282.9727; Found 282.9713.
1H NMR (400 MHz, DMSO-d6) δ 9.59 (s, 1H), 8.18 (d, J = 8.4 Hz,
1H), 8.10 (d, J = 8.0 Hz, 1H), 7.52 (s, 1H), 7.44 (t, J = 8.0 Hz, 1H). 13C
NMR (100 MHz, DMSO-d6) δ 137.6, 137.1, 133.7, 131.4, 130.8, 128.9,
114.5, 110.1, 99.0. HRMS (ESI) m/z: [M − HSO4]+ Calcd for
C9H5BrIN2 346.8675; Found 346.8676.
3g.
3k.
The reaction of 1-(3-bromophenyl)-5-iodoimidazole 2g (0.39 mmol,
137 mg) with an additional portion of Oxone in H2SO4 (scaled down to
0.39 mmol of 2g) according to the general procedure afforded 7-
bromobenzo[d]imidazo[5,1-b][1,3]iodazol-4-ium hydrogen sulfate 3g
as an off-white solid, 145 mg, yield: 84%. mp = 244−247 °C.
1H NMR (400 MHz, DMSO-d6) δ 9.20 (s, 1H), 8.69 (d, J = 2.0 Hz,
1H), 8.01 (d, J = 8.8 Hz, 1H), 7.71 (dd, J = 8.8, 2.0 Hz, 1H), 7.40 (s,
1H). 13C NMR (100 MHz, DMSO-d6) δ 136.3, 136.0, 132.8, 131.6,
131.1, 125.1, 120.1, 111.5, 98.6. HRMS (ESI) m/z: [M − HSO4]+
Calcd for C9H5BrIN2 346.8675; Found 346.8678.
The reaction of 1-(2-methylphenyl)-5-iodoimidazole 2k (0.5 mmol,
142 mg) with one portion of Oxone in H2SO4 according to the general
procedure afforded 8-methylbenzo[d]imidazo[5,1-b][1,3]iodazol-4-
ium hydrogen sulfate 3k as an off-white solid, 119 mg, yield: 63%.
mp = 215−217 °C.
1H NMR (400 MHz, DMSO-d6) δ 9.01 (s, 1H), 8.01 (d, J = 8.4 Hz,
1H), 7.66 (d, J = 7.2 Hz, 1H), 7.49 (s, 1H), 7.44 (t, J = 8.0 Hz, 1H), 2.79
(s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 138.1, 134.8, 134.1, 131.2,
129.0, 128.9, 127.8, 112.3, 97.7, 21.4. HRMS (ESI) m/z: [M − HSO4]+
Calcd for C10H8IN2 282.9727; Found 282.9731.
3h.
3l.
The reaction of 1-(3-methylphenyl)-5-iodoimidazole 2h (0.5 mmol,
142 mg) with one portion of Oxone in H2SO4 according to the general
procedure afforded 7-methylbenzo[d]imidazo[5,1-b][1,3]iodazol-4-
ium hydrogen sulfate 3h as a white solid, 165 mg, yield: 87%. mp =
245−246 °C.
The reaction of 1-(2-fluorophenyl)-5-iodoimidazole 2l (0.5 mmol, 145
mg) with an additional portion of Oxone in H2SO4 according to the
general procedure afforded 8-fluorobenzo[d]imidazo[5,1-b][1,3]-
iodazol-4-ium hydrogen sulfate 3l as an off-white solid, 118 mg,
yield: 61%. mp = 244−247 °C.
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1H NMR (400 MHz, DMSO-d6) δ 8.84 (d, J = 2.0 Hz, 1H), 7.97 (d, J
= 8.0 Hz, 1H), 7.83 (dd, J = 10.8, 8.4 Hz, 1H), 7.56 (td, J = 8.4, 5.2 Hz,
1H), 7.46 (s, 1H). 13C NMR (100 MHz, DMSO-d6) δ 152.3 (d, J = 252
Hz), 137.4 (d, J = 13 Hz), 131.3, 128.7 (d, J = 6 Hz), 127.1 (d, J = 3 Hz),
124.3 (d, J = 14 Hz), 119.1 (d, J = 18 Hz), 113.8, 98.9. 19F NMR (376
MHz, DMSO-d6) δ −120.2 to −120.1 (m). HRMS (ESI) m/z: [M −
HSO4]+ Calcd for C9H5FIN2 286.9476; Found 286.9473.
3m.
Oxone (0.325 mmol, 200 mg) was added under cooling with an ice−
water bath to the stirring solution of 1-(3,5-dimethylphenyl)-5-
iodoimidazole 2p (0.5 mmol. 149 mg) in H2SO4 (0.8 mL). After the
full conversion of the starting material, the reaction mass was diluted
with ice and water and only 1−1.5 mL of 9 M NaOH was added. Then
the reaction mass was diluted with water to the volume of 50 mL and KI
(1.5 equiv, 124 mg) in 2 mL of water was added. The precipitate was
filtered and washed with water and acetone to give 5,7-dimethylbenzo-
[d]imidazo[5,1-b][1,3]iodazol-4-ium iodide 3p as a yellow solid, 134
mg, yield: 63%. mp = 164−167 °C.
1H NMR (400 MHz, DMSO-d6) δ 9.15 (s, 1H), 7.95 (s, 1H), 7.55 (s,
1H), 7.14 (s, 1H), 2.51 (s, 3H), 2.40 (s, 3H). 13C NMR (100 MHz,
DMSO-d6) δ 141.9 139.3, 136.1, 134.4, 132.7, 129.9, 115.9, 114.6, 93.5,
22.9, 20.7. HRMS (ESI) m/z: [M − I]+ Calcd for C11H10IN2 296.9883;
Found 296.9883.
The reaction of 2-methyl-1-phenyl-5-iodoimidazole 2m (0.5 mmol,
142 mg) with one portion of Oxone in H2SO4 according to the general
procedure afforded 1-methylbenzo[d]imidazo[5,1-b][1,3]iodazol-4-
ium hydrogen sulfate 3m as an off-white solid, 154 mg, yield: 40%.
mp = 203−206 °C.
3q.
1H NMR (400 MHz, DMSO-d6) δ 8.16 (d, J = 8.0 Hz, 1H), 8.06 (d, J
= 8.0 Hz, 1H), 7.80 (t, J = 7.2 Hz, 1H), 7.55 (t, J = 7,6 Hz, 1H), 7.26 (s,
1H), 2.87 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 145.7, 135.6,
131.9, 131.4, 130.3, 128.0, 118.3, 111.7, 96.4, 16.9. HRMS (ESI) m/z:
[M − HSO4]+ Calcd for C10H8IN2 282.9727; Found 282.9751.
3n.
Oxone (0.325 mmol, 200 mg) was added under cooling with an ice−
water bath to the stirring solution of 4-methyl-1-phenyl-imidazole 2q
(0.5 mmol. 142 mg) in H2SO4 (0.8 mL). After the full conversion of the
starting material, the reaction mass was diluted with ice and water and
only 1−1.5 mL of 9 M NaOH was added. Then the reaction mass was
diluted with water to the volume of 50 mL and KI (1.5 equiv, 124 mg) in
2 mL of water was added. The yellow precipitate was filtered and
washed with water and acetone to give 3-methylbenzo[d]imidazo[5,1-
b][1,3]iodazol-4-ium iodide 3q as a yellow solid, 195 mg, yield: 95%.
mp = 126−129 °C.
The reaction of 1-(4-methoxyphenyl)-4-methyl-5-iodoimidazole 2n
(0.5 mmol, 157 mg) with an additional portion of Oxone (0.2 and 0.3 g,
respectively, for the first and second batch of the oxidant) in H2SO4 (0.8
mL for both portions) according to the general procedure afforded 6-
methoxy-3-methylbenzo[d]imidazo[5,1-b][1,3]iodazol-4-ium hydro-
gen sulfate 3n as a pale brown solid, 103 mg, yield: 50%. mp = 225−
227 °C.
1H NMR (400 MHz, DMSO-d6) δ 9.02 (s, 1H), 8.49 (dd, J = 8.4, 0.8
Hz, 1H), 8.20 (dd, J = 8.0, 1.6 Hz, 1H), 7.81−7.77 (m, 1H), 7.50 (ddd, J
= 8.4, 7.2, 1.2 Hz, 1H), 2.40 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ
138.0, 134.7, 133.6, 132.2, 131.4, 128.1, 116.8, 110.0, 97.0, 13.9. HRMS
(ESI) m/z: [M − I]+ Calcd for C10H8IN2 282.9727; Found 282.9731.
Synthesis of Iodonium Salt 3a on 2 mmol Scale. A 50 mL
round-bottom flask equipped with a stir bar was charged with 96%
H2SO4 (2.4 mL) and cooled to between 0 and 5 °C. Then, finely ground
1-phenyl-5-iodoimidazole 2a (2 mmol) was added, and the resulting
mixture was stirred for 20 min, followed by portionwise addition of
finely ground Oxone (1.3 equiv, 2.6 mmol, 0.8 g) over 5 min. The
stirring was continued for 1 h between 0 and 5 °C. Next, the ice−water
bath was removed and stirring was continued for 1 h at room
temperature. After full consumption of the initial material, as gauged by
TLC (hexane:EtOAc = 2:1), ice was added to the reaction mixture (5
g). Then, the mixture was diluted with cold water to the total volume of
25 mL. A 9 M NaOH solution was added dropwise with cooling by an
ice−water bath until the appearance of the precipitate (approximately 9
mL); the resulting suspension was allowed to stir for 1 h at room
temperature. The final solid was filtered and washed with cold water (2
× 10 mL) and Et2O (3 × 10 mL) and dried under vacuum to give
iodonium salt 3a as an off-white solid, 579 mg, yield: 79%.
Synthesis of Benz[d]imidazo[5,1-b]thiazoles 4a−4k. General
Procedure (Described for 0.25 mmol Scale). Reactions proceeded under
an argon atmosphere. A Schlenk tube equipped with a magnetic stir bar
was charged with cyclic iodonium salt 3, S8 (0.125 mmol, 32 mg), and
Cs2CO3 (1 mmol, 326 mg). After 3 cycles of vacuum/refill, anhydrous
DMSO (2.5 mL) had been added under a stream of argon, and the
mixture was allowed to react at 100 °C on the oil bath for 4 h. The
reaction mass was cooled to room temperature and diluted with water.
The aqueous layer was extracted with EtOAc. The combined organic
layer was dried over MgSO4, and the solvent was removed. The crude
product was purified by column chromatography, eluting with
hexane:EtOAc (10:1 → 2:1).
1H NMR (400 MHz, DMSO-d6) δ 8.11 (s, 1H), 7.82 (dd, J = 8.8, 2.8
Hz, 1H), 7.57 (d, J = 8.8 Hz, 1H), 7.16 (d, J = 2.4 Hz, 1H), 4.02 (s, 3H),
2.52 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 157.6, 148.9, 143.4,
138.4, 133.9, 128.2, 113.9, 106.6, 95.0, 57.9, 14.3. HRMS (ESI) m/z:
[M − HSO4]+ Calcd for C11H10IN2O 312.9832; Found 312.9838.
3o.
The reaction of 1-(3,5-dichlorophenyl)-5-iodoimidazole 2o (0.3 mmol,
102 mg) with an additional portion of Oxone in H2SO4 (scaled down to
0.3 mmol) according to the general procedure afforded 5,7-
dichlorobenzo[d]imidazo[5,1-b][1,3]iodazol-4-ium hydrogen sulfate
3o as an off-white solid, 110 mg, yield: 85%. mp = 205−208 °C.
1H NMR (400 MHz, DMSO-d6) δ 9.18 (s, 1H), 8.45 (s, 1H), 7.80 (s,
1H), 7.56 (s, 1H). 13C NMR (100 MHz, DMSO-d6) δ 137.3, 137.1,
136.7, 133.9, 133.3, 126.8, 115.8, 99.5, 95.8. HRMS (ESI) m/z: [M −
HSO4]+ Calcd for C9H4Cl2IN2 336.8791; Found 336.8817.
Synthesis of 5,7-Dimethylbenzo[d]imidazo[5,1-b][1,3]-
iodazol-4-ium Iodide 3p and 3-Methylbenzo[d]imidazo[5,1-
b][1,3]iodazol-4-ium Iodide 3q. 3p.
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4a.
The reaction of iodonium salt 3e (0.25 mmol, 111 mg) according to the
general procedure after column chromatography (hexane:EtOAc (10:1
→ 2:1)) afforded 6-bromobenzo[d]imidazo[5,1-b]thiazole 4e as a
yellowish solid, 40 mg, yield: 63%. mp = 186−188 °C.
1H NMR (400 MHz, DMSO-d6) δ 8.78 (s, 1H), 8.21 (d, J = 1.6 Hz,
1H), 8.06 (d, J = 8.4 Hz, 1H), 7.69 (dd, J = 8.4, 2.0 Hz, 1H), 7.14 (s,
1H). 13C NMR (100 MHz, DMSO-d6) δ 135.0, 130.3, 129.1, 128.5,
127.7, 127.3, 118.5, 117.5, 115.3. HRMS (ESI) m/z: [M + Na]+ Calcd
for C9H5BrN2SNa 274.9249; Found 274.9248.
The reaction of iodonium salt 3a (0.25 mmol, 91.5 mg) according to
the general procedure after column chromatography (hexane:EtOAc
(10:1 → 2:1)) afforded benzo[d]imidazo[5,1-b]thiazole 4a as a pale
yellow solid, 33.5 mg, yield: 77%. mp = 99−101 °C.
4f.
1H NMR (400 MHz, DMSO-d6) δ 8.78 (s, 1H), 8.10 (d, J = 8.0 Hz,
1H), 7.89 (d, J = 8.0 Hz, 1H), 7.51−7.48 (m, 1H), 7.42−7.38 (m, 1H),
7.14 (s, 1H). 13C NMR (100 MHz, DMSO-d6) δ 132.6, 130.9, 128.2,
127.5, 126.3, 125.8, 124.9, 118.3, 113.8. HRMS (ESI) m/z: [M + Na]+
Calcd for C9H6N2SNa 197.0144; Found 197.0145.
4b.
The reaction of iodonium salt 3f (0.25 mmol, 95 mg) according to the
general procedure after column chromatography (hexane:EtOAc (10:1
→ 2:1)) afforded 6-methylbenzo[d]imidazo[5,1-b]thiazole 4f as a waxy
pale yellow solid, 37 mg, yield: 79%.
1H NMR (400 MHz, MeOD-d4) δ 8.54 (s, 1H), 7.75 (d, J = 8.4 Hz,
1H), 7.47 (s, 1H), 7.22 (d, J = 8.4 Hz, 1H), 7.05 (s, 1H), 2.41 (s, 3H).
13C NMR (100 MHz, MeOD-d4) δ 137.8, 134.4, 130.4, 130.0, 128.5,
128.2, 125.4, 118.3, 114.2, 21.3. HRMS (EI) m/z: [M]+· Calcd for
C10H8N2S 188.0403; Found 188.0403.
The reaction of iodonium salt 3b (0.25 mmol, 96 mg) according to the
general procedure after column chromatography (hexane:EtOAc (10:1
→ 2:1)) afforded methyl benzo[d]imidazo[5,1-b]thiazole-6-carbox-
ylate 4b as a waxy pale brown solid, 29 mg, yield: 50%.
1H NMR (400 MHz, DMSO-d6) δ 8.92 (br.s, 1H), 8.55 (s, 1H), 8.22
(d, J = 8.4 Hz, 1H), 8.08 (d, J = 8.4 Hz, 1H), 7.22 (br.s, 1H), 3.89 (s,
3H). 13C NMR (100 MHz, DMSO-d6) δ 165.4, 134.1, 133.6, 127.6,
127.0, 126.4, 113.8, 52.5. HRMS (EI) m/z: [M]+· Calcd for
C11H8N2O2S 232.0301; Found 232.0301.
4g.
4c.
The reaction of iodonium salt 3g (0.25 mmol, 111 mg) according to the
general procedure after column chromatography (hexane:EtOAc (10:1
→ 2:1)) afforded 7-bromobenzo[d]imidazo[5,1-b]thiazole 4g as a
waxy solid, 30 mg, yield: 48%.
1H NMR (400 MHz, DMSO-d6) δ 8.79 (s, 1H), 8.47 (d, J = 2.0 Hz,
1H), 7.86 (d, J = 8.4 Hz, 1H), 7.57 (dd, J = 8.4, J = 2.0 Hz, 1H), 7.13 (s,
1H). 13C NMR (100 MHz, DMSO-d6) δ 132.2, 132.1, 128.6, 128.4,
128.1, 126.6, 118.5, 118.5, 116.9. HRMS (EI) m/z: [M]+· Calcd for
C9H5BrN2S 251.9351; Found 251.9357.
The reaction of iodonium salt 3c (0.25 mmol, 96 mg) according to the
general procedure after column chromatography (hexane:EtOAc (10:1
→ 2:1)) afforded 6-fluorobenzo[d]imidazo[5,1-b]thiazole 4c as a waxy
yellow solid, 34 mg, yield: 71%.
1H NMR (400 MHz, DMSO-d6) δ 8.75 (s, 1H), 8.13 (dd, J = 8.8, 4.8
Hz, 1H), 7.88 (dd, J = 9.2, 2.4 Hz, 1H), 7.41−7.36 (m, 1H), 7.13 (s,
1H). 13C NMR (100 MHz, DMSO-d6) δ 159.5(d, J = 240 Hz), 134.5
(d, J = 10 Hz), 127.9, 118.7, 114.8 (d, J = 10 Hz), 113.6 (d, J = 24 Hz),
111.9 (d, J = 27 Hz). 19F NMR (376 MHz, DMSO-d6) δ −116.0 to
−115.9 (m). HRMS (ESI) m/z: [M + H]+ Calcd for C9H6FN2S
193.0230; Found 193.0230.
4h.
The reaction of iodonium salt 3h (0.25 mmol, 95 mg) according to the
general procedure after column chromatography (hexane:EtOAc (10:1
→ 2:1)) afforded 7-methylbenzo[d]imidazo[5,1-b]thiazole 4h as a
waxy solid, 42 mg, yield: 89%. mp = 128−130 °C.
4d.
1H NMR (400 MHz, MeOD-d4) δ 8.57 (s, 1H), 7.74 (s, 1H), 7.53
(d, J = 8.0 Hz, 1H), 7.19 (d, J = 8.0 Hz, 1H), 7.06 (s, 1H), 2.46 (s, 3H).
13C NMR (100 MHz, MeOD-d4) δ 138.1, 132.5, 131.1, 130.4, 128.4,
125.1, 118.3, 118.2, 115.1, 21.3. HRMS (EI) m/z: [M]+· Calcd for
C10H8N2S 188.0403; Found 188.0403.
The reaction of iodonium salt 3d (0.25 mmol, 100 mg) according to the
general procedure after column chromatography (hexane:EtOAc (10:1
→ 2:1)) afforded 6-chlorobenzo[d]imidazo[5,1-b]thiazole 4d as a pale
yellow solid, 39 mg, yield: 63%. mp = 165−168 °C (recrystallized
sample).
4i.
1H NMR (400 MHz, MeOD-d4) δ 8.61 (s, 1H), 7.89 (d, J = 8.4 Hz,
1H), 7.76 (d, J = 2.0 Hz, 1H), 7.42 (dd, J = 8.8, 2.0 Hz, 1H), 7.09 (s,
1H). 13C NMR (100 MHz, MeOD-d4) δ 136.3, 132.6, 131.3, 130.1,
129.0, 127.5, 125.3, 118.8, 115.6. HRMS (ESI) m/z: [M + H]+ Calcd
for C9H6ClN2S 208.9935; Found 208.9936.
The reaction of iodonium salt 3k (0.25 mmol, 95 mg) according to the
general procedure after column chromatography (hexane:EtOAc (10:1
→ 2:1)) afforded 8-methylbenzo[d]imidazo[5,1-b]thiazole 4i as a waxy
pale yellow solid, 26 mg, yield: 55%.
4e.
1H NMR (400 MHz, DMSO-d6) δ 8.64 (s, 1H), 7.74−7.69 (m, 1H),
7.31−7.29 (m, 2H), 7.18 (s, 1H), 2.73 (s, 3H). 13C NMR (100 MHz,
DMSO-d6) δ 132.7, 130.6, 129.9, 128.2, 127.8, 125.5, 125.1, 122.2,
7175
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J. Org. Chem. 2021, 86, 7163−7178

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pubs.acs.org/joc
Article
117.7, 19.5. HRMS (EI) m/z: [M]+· Calcd for C10H8N2S 188.0403;
Found 188.0403.
Authors
Nikita S. Antonkin − Research School of Chemistry and Applied
Biomedical Sciences, Tomsk Polytechnic University, Tomsk
634050, Russian Federation
4j.
Yulia A. Vlasenko − Research School of Chemistry and Applied
Biomedical Sciences, Tomsk Polytechnic University, Tomsk
634050, Russian Federation
Akira Yoshimura − Research School of Chemistry and Applied
Biomedical Sciences, Tomsk Polytechnic University, Tomsk
634050, Russian Federation
Vladimir I. Smirnov − A. E. Favorsky Irkutsk Institute of
Chemistry, Siberian Branch of the Russian Academy of
Sciences, Irkutsk 664033, Russian Federation
Tatyana N. Borodina − A. E. Favorsky Irkutsk Institute of
Chemistry, Siberian Branch of the Russian Academy of
Sciences, Irkutsk 664033, Russian Federation
Viktor V. Zhdankin − Research School of Chemistry and
Applied Biomedical Sciences, Tomsk Polytechnic University,
Tomsk 634050, Russian Federation; Department of Chemistry
and Biochemistry, University of Minnesota Duluth, Duluth,
Minnesota 55812, United States
The reaction of iodonium salt 3o (0.2 mmol, 87 mg) according to the
general procedure (scaled down to 0.2 mmol) after column
chromatography (hexane:EtOAc (10:1 → 2:1)) afforded 5,7-
dichlorobenzo[d]imidazo[5,1-b]thiazole 4j as a waxy yellow solid,
24.5 mg, yield: 50%.
1H NMR (400 MHz, DMSO-d6) δ 8.81 (s, 1H), 8.38 (d, J = 2.0 Hz,
1H), 7.76 (d, J = 1.6 Hz, 1H), 7.20 (d, J = 1.2 Hz, 1H). 13C NMR (100
MHz, DMSO-d6) δ 132.6, 131.5, 131.3, 129.2, 128.0, 126.9, 125.0,
119.3, 113.3. HRMS (ESI) m/z: [M + H]+ calcd for C9H5Cl2N2S
242.9545; Found 242.9539.
4k.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00483
The reaction of iodonium salt 3p (0.25 mmol, 106 mg) according to the
general procedure after column chromatography (hexane:EtOAc (10:1
→ 2:1)) afforded 5,7-dimethylbenzo[d]imidazo[5,1-b]thiazole 4k as a
waxy pale yellow solid, 36 mg, yield: 71%.
Notes
The authors declare no competing financial interest.
The presented report was initially published as a preprint:
Antonkin, N.; Vlasenko, Y.; Yoshimura, A.; Smirnov, V.;
Borodina, T.; Zhdankin, V.; Yusubov, M.; Shafir, A.; Postnikov,
P. Preparation and Synthetic Applicability of Novel Imidazole-
Containing Cyclic Iodonium Salts. ChemRxiv. February 23,
2021. DOI: 10.26434/chemrxiv.14077565.v1.
1H NMR (400 MHz, MeOD-d4) δ 8.51 (s, 1H), 7.52 (s, 1H), 7.05 (s,
1H), 6.99 (s, 1H), 2.41 (s, 3H), 2.33 (s, 3H). 13C NMR (100 MHz,
MeOD-d4) δ 138.2, 134.8, 132.2, 130.7, 130.2, 128.8, 128.6, 118.3,
112.5, 21.3, 19.5. HRMS (ESI) m/z: [M + H]+ Calcd for C11H11N2S
203.0637; Found 203.0648.
ASSOCIATED CONTENT
■
sı
* Supporting Information
ACKNOWLEDGMENTS
■
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00483.
The heterocyclization study was supported by the Russian
Science Foundation (project No. 17-73-20066). Y.A.V. kindly
acknowledges the financial support from the Russian Founda-
tion of Basic Research for the development of oxidative
cyclization process (project No. 20-33-90007). This work was
funded by Spain’s MINECO (CTQ2017-86936-P), AGAUR
(2017 SGR 01051), and additional support from CSIC. The
authors would like to acknowledge the Multi-Access Chemical
Research Center SB RAS (N.N. Vorozhtsov Novosibirsk
Institute of Organic Chemistry) and the Center for Chemical
Analysis and Materials Research of Saint Petersburg State
University for analytical measurements. X-ray structural results
were obtained using the material and technical base of the Baikal
Analytical Center for Collective Use of the SB RAS.
Single-crystal X-ray diffraction data for compounds 3c
and 3j and NMR spectra for all compounds (PDF)
Accession Codes
CCDC 2058419 and 2058420 contain the supplementary
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.
AUTHOR INFORMATION
■
Corresponding Authors
REFERENCES
Mekhman S. Yusubov − Research School of Chemistry and
Applied Biomedical Sciences, Tomsk Polytechnic University,
Tomsk 634050, Russian Federation; Email: yusubov@
mail.ru
■
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