One-Pot, Two-Step Metal and Acid-Free Synthesis of Trisubstituted Imidazole Derivatives via Oxidation of Internal Alkynes Using an Iodine/DMSO System

Article abstract of DOI:10.1002/ejoc.201801584

A one-pot, two-step, simple, efficient and eco-friendly oxidation of internal alkynes as a key step towards the synthesis of 2,4,5-trisubstituted imidazoles, using an inexpensive I₂/DMSO system, has been reported. This metal and acid-free synthesis proceeded smoothly to furnish a variety of synthetically useful trisubstituted imidazoles in moderate to excellent yields. In an effort to demonstrate the potential future applications of this system, a double oxidation study was undertaken and the desired trisubstituted imidazoles obtained in good to moderate yields.

Full text of DOI:10.1002/ejoc.201801584

DOI: 10.1002/ejoc.201801584
Full Paper
Imidazole Synthesis
One-Pot, Two-Step Metal and Acid-Free Synthesis of
Trisubstituted Imidazole Derivatives via Oxidation of Internal
Alkynes Using an Iodine/DMSO System
Shivani Naidoo[a] and Vineet Jeena*[a]
Abstract: A one-pot, two-step, simple, efficient and eco- thetically useful trisubstituted imidazoles in moderate to excel-
friendly oxidation of internal alkynes as a key step towards the lent yields. In an effort to demonstrate the potential future ap-
synthesis of 2,4,5-trisubstituted imidazoles, using an inexpen- plications of this system, a double oxidation study was under-
sive I2/DMSO system, has been reported. This metal and acid- taken and the desired trisubstituted imidazoles obtained in
free synthesis proceeded smoothly to furnish a variety of syn- good to moderate yields.
Introduction
ical activity such as inhibitors of p38 MAP kinase,[13] B-Raf kin-
ase[14] and biosynthesis of interleukin 1 (IL-1).[15] Trisubstituted
imidazoles, in particular, have rich medicinal applications and
are known to act as good α-glucosidase inhibition agents.[16]
These substituted imidazoles are also known to possess good
photophysical properties such as organic light-emitting diodes
(OLEDs)[17] and, in addition, can be used in photography as
photosensitive compounds.[18]
Consequently, a plethora of routes have been devised for the
synthesis of these valuable trisubstituted imidazole deriva-
tives[19] and, traditionally, the cardinal synthesis towards trisub-
stituted imidazole derivatives involves the condensation of an
α-diketone, aldehyde and ammonium acetate in the presence
of a metal or acid catalyst (Scheme 1A).[20] An alternate strategy
by Wang and co-workers utilized stoichiometric pivalic acid as
an oxidant, together with a solvent mixture of DMSO/water to
promote the synthesis of imidazole derivatives via alkyne oxid-
ation (Scheme 1B).[21] However, most of the above methods
Oxidation reactions form an area of paramount significance
within the realm of synthetic organic chemistry.[1] These pro-
found reactions allow chemists to design attractive methodolo-
gies that allow for the formation of carbon-carbon (C–C) bonds
or the introduction of one or more electronegative atoms onto
a molecule.[2] This has led to the steadily increasing develop-
ment of novel, environmentally benign, inexpensive and high
yielding oxidation protocols, thus allowing for the formation of
complex molecules.[3]
There has been a long-standing interest in the development
of internal alkyne oxidation to 1,2-diketones, as this is an impor-
tant synthetic transformation that allows the generated diket-
ones to be readily converted into various biologically active
compounds.[4] Internal alkynes can be readily oxidized to 1,2-
diketones by several methods[5] such as; the use of potassium
permanganate,[6] ruthenium,[7] chromium[8] and cobalt oxid-
ants[9] and a sulfur trioxide-dioxane complex[10] to name but a
few. However, most of these methods suffer from several draw-
backs such as harsh reaction conditions, displeasing product
yields, tedious isolation procedures and the use of expensive
and detrimental metal precursors.
These newly transformed diketones lead to the synthesis of
valuable compounds such as N-heterocycles, which occupy an
important place in the realm of synthetic organic chemistry and
natural products research, as they are considered to be signifi-
cant biological moieties and important chemical building
blocks in the pharmaceutical and agrochemical industries.[11] Of
those N-heterocyclic compounds, the trisubstituted imidazole
motif is of utmost importance as it is an essential component
in many natural products[12] and displays a vast range of biolog-
[a] School of Chemistry and Physics, University of KwaZulu-Natal,
Scottsville, Pietermaritzburg, 3209, South Africa
E-mail: Jeenav1@ukzn.ac.za
ORCID(s) from the author(s) for this article is/are available on the WWW
under https://doi.org/10.1002/ejoc.201801584.
Scheme 1. Synthetic procedures towards 2,4,5-trisubstituted imidazoles.
1 © 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Full Paper
suffer from several drawbacks such as complex and laborious
work-up procedures, use of toxic transition metal catalysts, pro-
duce a large amount of waste, strongly acidic conditions, the
occurrence of side reactions, low yields and the use of expen-
sive reagents. Thus, there is a dire need for an efficient and
environmentally benign protocol for the synthesis of substi-
tuted imidazoles. Recently, molecular iodine has gained sub-
stantial interest due to its inexpensive, nontoxic and nonmetal-
lic nature, and has thus become an important reagent for or-
ganic functional group transformations.[22] Dimethyl sulfoxide
(DMSO) is an inexpensive, low-toxic solvent that has been used
extensively as an oxidant[23] and synthon[24] in many renowned
reactions such as the Swern oxidation,[25] Pfitzner-Moffatt oxid-
ation[26] and the Corey-Chaykovsky epoxidation and cycloprop-
anation.[27] The combination of molecular iodine and DMSO has
revolutionized synthetic methodology especially those related
to oxidative processes.[28]
Table 1. Optimization of reaction conditions for the synthesis of 2,4,5-tri-
phenyl-1H-imidazole (3a).[a]
Entry
Conditions
Solvent (2 mL)
Yield (%)[b]
1[c]
2
3
4
5
6
7
8
9
10
11[d]
12[e]
13[f]
14
15
16
17
18[g]
19[h]
I2/DMSO
I2/DMSO
I2/DMSO
I2/DMSO
I2/DMSO
I2/DMSO
I2/DMSO
I2/DMF
–
–
N.R
39
N.R
N.R
N.R
48
Propan-2-ol
Water
Diethyl ether
Methanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
90
N.R
N.R
N.R
77
40
31
N.R
N.R
N.R
N.R
14
I2/MeCN
I2/THF
I2/DMSO
I2/DMSO
I2/DMSO
I2O5/DMSO
IBX/DMSO
I2
DMSO
I2/DMSO
I2/DMSO
Herein we report an alternative method for the synthesis of
imidazole derivatives using an internal alkyne, aldehyde, and
ammonium acetate under metal and acid-free conditions
(Scheme 1C).
11
Results and Discussion
[a] Reaction conditions: Step 1: 1a (0.5 mmol), I2 (1.5 equiv.)/DMSO (1 mL),
1 h, 130 °C. Step 2: 2a (0.5 mmol), NH4OAc (10 equiv.), solvent (2 mL), 2 h,
100 °C. [b] Isolated yield. [c] One-pot, one-step reaction, 100 °C, 2 h. [d] I2
(1 equiv.)/DMSO (1 mL), 100 °C, 2 h. [e] I2 (0.5 equiv.)/DMSO (1 mL), 100 °C,
2 h. [f] I2 (0.1 equiv.)/DMSO (1 mL), 100 °C, 2 h. [g] NH4OAc (5 equiv.).
[h] NH4OAc (2 equiv.). N. R = No reaction.
In search of optimal conditions, the one-pot reaction between
diphenylacetylene (1a), benzaldehyde (2a) and ammonium
acetate in DMSO for 2 h in the presence of 1.5 equivalents of
molecular iodine (I2) was examined, however, the desired prod-
uct 3a was not obtained (Table 1, entry 1). Thereafter, the reac-
tion was attempted in a one-pot two-step manner, the di-
phenylacetylene was heated in DMSO for 1 h at 130 °C in the (Table 1, entry 16) or I2 (Table 1, entry 17). Numerous trisubsti-
presence of 1.5 equivalents of molecular iodine (I2). Thereafter, tuted imidazole synthetic procedures use fluctuating amounts
benzaldehyde and ammonium acetate were added, and the of ammonium acetate,[31] therefore, an attempt to decrease the
mixture was left to react for a further 2 h at 100 °C.
amount of ammonium acetate was made. When 5 and 2 equiv-
alents were used, lower isolated yields of 14 % and 11 % were
obtained (Table 1, entries 18–19). Therefore, the conditions de-
scribed in (Table 1, entry 7), were found to be optimal and
allowed for the maximum formation of the desired product 3a.
(See the Supporting Information for additional temperature,
solvent volume and iodo source variation studies (S2-S3). Hav-
ing optimized the reaction conditions, the scope of the devel-
oped system was assessed by varying the internal alkynes and
aldehydes, the ensuing results of which are listed in Table 2.
The coupling of benzaldehyde derivatives, bearing para-sub-
Encouragingly, the desired product, 2,4,5-triphenyl-1H-imid-
azole (3a) was obtained in a 39 % isolated yield (Table 1, entry
2). The coupling reaction of trisubstituted imidazoles is known
to be solvent specific,[29] therefore, to promote this reaction, a
range of organic solvents were added to encourage cyclization,
however, no product was isolated in the presence of propan-2-
ol, water and diethyl ether (Table 1, entries 3–5). When meth-
anol was used, the desired product was formed in a 48 % iso-
lated yield (Table 1, entry 6). We then turned our attention to-
ward using ethanol, as many imidazole synthetic reactions are
known to proceed well in the presence of this solvent[30] and, stituted electron-withdrawing and electron-donating substitu-
to our delight, the yield of the isolated product increased to ents, with 1a afforded 2,4,5-trisubstituted imidazoles (Table 2,
90 % (Table 1, entry 7).To determine if DMSO is the ideal cou- entries 3a–3e) in high yields of 83 % to 95 %. Good imidazole
pling partner for I2, we examined DMF, MeCN and THF (Table 1, yields of 63 % to 73 %, were obtained with benzaldehyde sub-
entries 8–10), however, there was no product formation sug- stituted at the ortho position (Table 2, entries 3f–3 h). Similarly,
gesting that DMSO is essential for this reaction. The loading of meta substituted nitrobenzaldehyde resulted in 2-(3-nitro-
iodine was decreased, to 1, 0.5 and 0.1 equivalents, however, phenyl)-4,5-diphenyl-1H-imidazole (Table 2, entry 3i) in a favor-
the formation of 3a was substantially reduced to isolated yields able yield of 72 %. Encouraged by these results, and to diversify
of 77 %, 40 % and 31 %, respectively (Table 1, entries 11–13). our substrates, a bulkier aldehyde such as 2-naphthaldehyde
Other iodine containing nonmetal catalysts such as; iodine was employed which delivered the resulting 2-(naphthalen-2-
pentoxide (I2O5) and 2-iodobenzoic acid (IBX) were screened yl)-4,5-diphenyl-1H-imidazole in an excellent yield of 85 %
(Table 1, entries 14–15) and both catalysts resulted in no prod- (Table 2, entry 3j). To expand the scope of our methodology,
uct formation. There was no reaction in the absence of DMSO aliphatic aldehydes were employed, however, the correspond-
Eur. J. Org. Chem. 0000, 0–0
www.eurjoc.org
2
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Table 2. Substrate scope of 2,4,5-trisubstituted-1H-imidazoles with various
ined. Unfortunately, 1-phenyl-1-propyne and 2-butyne resulted
in no product formation, (Table 2, 3o-3p), which is probably
due to the reduced nucleophilicity of these substrates.[33]
Thereafter, 1,2-bis(4-bromophenyl)acetylene reacted smoothly
to successfully afford 4,5-bis(4-bromophenyl)-2-phenyl-1H-imid-
azole in a favorable yield of 60 % (3q). The coupling between
1-(4-chlorophenyl)-2-phenylacetylene with benzaldehyde deriv-
atives also produced 2,4,5-triarylimidazoles, 3r–3t as a mixture
of tautomers, due to the presence of the fluid hydrogen on the
nitrogen atom, in satisfactory yields of 68 % to 72 %.
alkynes and aldehydes.[a]
Next, we turned our attention towards the convergent inte-
gration of two domino sequences beginning from the internal
alkyne and primary alcohols to produce trisubstituted imidaz-
oles. The rationale behind this synthetic approach was to com-
mence from two unusual starting materials (internal alkyne and
primary alcohol) which could be converted into the diketone
and aldehyde using the I2/DMSO system, which would then
serve as intermediates en route to the target imidazole. As a
preliminary experiment, the oxidation of diphenylacetylene and
benzyl alcohol was carried out, in the same reaction vessel, in
the presence of 2 equivalents of I2 in DMSO for 24 h, thereafter,
ammonium acetate together with ethanol was added and the
mixture was left to react for a further 2 h. To our absolute de-
light, this reaction proceeded smoothly and furnished the corre-
sponding 2,4,5-triphenyl-1H-imidazole in an 81 % isolated yield
(Scheme 2). With this exciting result in hand, we decided to test
this double oxidation reaction with an aliphatic alcohol, which
although successful, produced the target imidazole in a moder-
ate 20 % isolated yield. These results illustrate that the I2/DMSO
system can effect multiple chemical transformations, in the
same reaction vessel, and can become a key component of fu-
ture convergent integration syntheses and may develop into a
valuable synthetic strategy towards a range of fascinating com-
pounds.
[a] Reaction conditions: Step 1: 1 (0.5 mmol), I2 (1.5 equiv.)/DMSO (1 mL), 1 h,
130 °C. Step 2: 2 (0.5 mmol), NH4OAc (10 equiv.), EtOH (2 mL), 3 h, 100 °C.
[b] Isolated yield. [c] Step 2: 24 h. [d] Step 1: 24 h. [e] Mixture of tautomers
(see the Supporting Information for details).
Scheme 2. Convergent synthesis of 2,4,5-trisubstituted imidazoles.
ing alkylated imidazoles were synthesized in low yields of 18 %
to trace amounts (Table 2, entry 3k and 3l). This result is con-
To gain insight into the reaction mechanism, a number of
sistent with literature, as aliphatic aldehydes are not commonly control experiments were carried out (Scheme 3). First, diphen-
examined in trisubstituted imidazole synthesis,[32] and, when ylacetylene (1a) was oxidized with I2/DMSO at 130 °C for 1 h,
they are, often result in low yields. More encouraging, was the to afford benzil in a 93 % isolated yield, confirming that the
use of heterocyclic aldehydes, indole-3-carboxaldehyde and 2- diketone is indeed an intermediate in this transformation
furfural, which successfully proceeded to generate the desired (Scheme 3, eqn. (1)). Next, a mixture of benzil, benzaldehyde
products albeit in modest yields of 54 % and 40 %, respectively and ammonium acetate, was treated with I2 and ethanol and
(Table 2, entries 3m and 3n). Next, the coupling reactions be- afforded 3a in a yield of 94 %, while, in the absence of iodine,
tween benzaldehyde and various internal alkynes were exam- no product was detected, indicating that iodine plays a vital
Eur. J. Org. Chem. 0000, 0–0
www.eurjoc.org
3
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
role in the coupling reaction leading to the trisubstituted imid- replicated, with H2O and toluene as a solvent mixture, the reac-
azole[34] (Scheme 3, eqn. (2)). The radical scavenger 2,2,6,6-tet- tion did not proceed as only starting material was observed,
ramethyl-1-piperidinyloxy (TEMPO) was added to the reaction suggesting that trace H2O in DMSO does not play a role in the
mixture under the standard conditions and 3a was formed in oxidation of the internal alkyne (Scheme 3, eq. (5)). Finally, we
an 89 % isolated yield, suggesting that the reaction does not speculated that the iodoketone was an intermediate in this syn-
proceed via a radical pathway (Scheme 3, eqn. (3)). The test thetic route as we could rationalize its formation mechanisti-
reaction was also carried out under an N2 atmosphere, which cally, and proceeded to synthesize this compound using a liter-
resulted in 3a being formed in an 87 % isolated yield, indicating ature process[35] and test its reactivity. Firstly, the iodoketone
that the oxidation is not dependent on O2 from the atmosphere was heated in anhydrous DMSO, which resulted in the forma-
(Scheme 3, eqn. (4)).
tion of benzil in an excellent yield of 90 % (Scheme 3, eqn. (6)).
However, when the same reaction was attempted in a solvent
mixture of H2O and toluene, no product was obtained
(Scheme 3, eqn. (6)). Lastly, we reacted the iodoketone to form
benzil, and upon the addition of benzaldehyde and ammonium
acetate, led to the formation of 3a in an 87 % isolated yield
(Scheme 3, eqn. (7)). These results suggest that the iodoketone
is an important intermediate in the alkyne oxidation and it re-
acts with DMSO to generate the diketone, which upon addition
of the aldehyde and ammonium acetate leads to the observed
imidazole.
Based on the results of our control experiments and previous
literature reports,[36] a likely mechanism is outlined in Scheme 4.
It is feasible that the reaction begins with the activation of the
triple bond of the alkyne by iodine to furnish the iodonium
intermediate A. The addition of DMSO on A allows for the for-
mation of the iodide intermediate B, simultaneously dispelling
the weakly basic dimethyl sulfide (Me2S).[37] The generated
iodoketone is immediately trapped by a molecule of DMSO, to
form intermediate C, which progresses to form the expected
1,2-diketone while expelling a second molecule of Me2S. There-
after, A and the aldehyde (2) are concurrently activated by
Scheme 3. Control experiments for I2/DMSO catalysed trisubstituted imidaz-
ole synthesis.
The next set of control experiments was conducted to deter-
mine the source of oxygen in the diketone, which could origi-
nate from either the DMSO or trace H2O present in DMSO. In
the presence of, freshly distilled, anhydrous DMSO, 3a was syn-
thesized in an 82 % isolated yield, suggesting that DMSO is
the dominant source of oxygen. When the same reaction was
Scheme 4. Plausible mechanism for the synthesis of trisubstituted imidazoles.
4 © 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0
www.eurjoc.org

Full Paper
7.41–7.40 (m, 1 H), 7.34–7.30 (m, 2 H), 7.26–7.23 (m, 1 H) ppm. 13C
NMR (100 MHz, [D6]DMSO): δ = 145.0, 137.9, 135.5, 132.1, 131.4,
130.1, 129.13, 129.1, 128.9, 128.7, 128.3, 127.6, 127.1, 121.9 ppm. IR:
iodine and upon reaction with ammonium acetate, form imine
intermediates E and F. Both imine intermediates undergo cyclo-
condensation to afford the desired 2,4,5-trisubstituted imidaz-
ole 3 (Scheme 4).
ν = 3594, 2640, 2195, 1599, 1478, 1125, 765 cm–1. ESI-MS (m/z) 375
˜
[M + H]+.
2-(4-Chlorophenyl)-4,5-diphenyl-1H-imidazole (3c):[39,40] Yield
1
155.48 mg (94 %); white solid; m.p. 262–264 °C. H NMR (400 MHz,
Conclusions
[D6]DMSO): δ = 12.77 (s, 1 H), 8.13–8.10 (d, J = 8.5 Hz, 2 H), 7.57–
7.55 (d, J = 8.96 Hz, 4 H), 8.53–8.51 (m, 2 H), 7.48–7.44 (m, 2 H),
In summary, we have described a simple, efficient, eco-friendly
and inexpensive methodology for the synthesis of 2,4,5-trisub- 7.41–7.38 (m, 1 H), 7.34–7.30 (m, 2 H), 7.26–7.22 (m, 1 H) ppm. 13C
NMR (100 MHz, [D6]DMSO): δ = 145.3, 138.2, 135.9, 133.6, 131.8,
stituted imidazoles from various internal alkynes, aldehydes,
and ammonium acetate via an I2/DMSO oxidation system. The
developed system provides a convenient and practical route
that can be applied to a range of substrates, making this imid-
azole synthetic technique an alternative approach that could
replace conventional processes. Furthermore, this system was
applicable to a convergent integration domino sequence of an
internal alkyne and primary alcohol, resulting in the formation
of trisubstituted imidazoles. Supplementary studies expanding
the scope of this methodology as well as in-depth mechanistic
studies are underway in our laboratories and will be reported
in due course.
130.1, 129.6, 129.5, 129.3, 128.7, 128.0, 127.7, 127.5 ppm. IR: ν =
˜
2837, 1480, 1127, 763 cm–1. ESI-MS (m/z) 375 [M + H]+.
2-(4-Fluorophenyl)-4,5-diphenyl-1H-imidazole (3d):[39,40] Yield
1
130.46 mg (83 %); white solid; m.p. 262–264 °C. H NMR (400 MHz,
[D6]DMSO): δ = 12.69 (s, 1 H), 8.16–8.12 (m, 2 H), 7.54 (m, 4 H),
7.49–7.23 (m, 8 H) ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 163.8,
161.4, 145.2, 128.9, 128.2, 127.9 (d, J
= 6.57 Hz), 127.5 (d, J
=
C,F
C,F
2.7 Hz), 116.1 (d, J
= 21.3 Hz) ppm. IR: ν = 2639, 1607, 1491,
C,F
˜
1223, 1159 cm–1. ESI-MS (m/z) 315 [M + H]+.
2-(4-Methoxyphenyl)-4,5-diphenyl-1H-imidazole (3e):[38] Yield
146.9 mg (90 %); white solid; m.p. 230–233 °C. 1H NMR (400 MHz,
[D6]DMSO): δ = 12.51 (s, 1 H), 8.05–8.03 (d, J = 8.84 Hz, 2 H), 7.54–
7.25 (m, 10 H), 7.07–7.05 (d, J = 8.83 Hz, 2 H), 3.83 (s, 3 H) ppm. 13
C
NMR (100 MHz, [D6]DMSO): δ = 159.9, 146.1, 137.1, 135.9, 131.7,
Experimental Section
128.8, 127.6, 127.2, 123.6, 114.6, 55.7 ppm. IR: ν = 2960, 2095, 1609,
˜
1490, 1241, 1174 cm–1. ESI-MS (m/z) 327 [M + H]+.
General Remarks: All reagents were purchased and used without
further purification. All 1H and 13C nuclear magnetic resonance
(NMR) spectra were recorded on the Bruker Avance III spectrometer
operating at 400 MHz. Chemical shifts (δ) were reported in ppm
using the dimethyl sulfoxide-d6 ([D6]DMSO) residual peak (δ 2.50)
for 1H NMR spectroscopy. Chemical shifts for 13C NMR were re-
ported relative to [D6]DMSO (δ 39.51). The following abbreviations
were used to describe peak splitting patterns: br = broad, s = sin-
glet, d = doublet, t = triplet, q = quartet, m = multiplet. Coupling
constants, J, were reported in Hertz (Hz). High-resolution electron-
spray ionization (ESI) mass spectra were recorded in a time of flight
(TOF) micromass spectrometer. Infra-red (IR) spectra were recorded
on the Carey 630 FTIR. Absorption maxima are expressed in wave-
numbers (cm–1). Melting points were determined using a Kofler hot-
stage melting apparatus.
2-(2-Nitrophenyl)-4,5-diphenyl-1H-imidazole
(3f):[41]
Yield
107.53 mg (63 %); yellow solid; m.p. 268–272 °C. 1H NMR (400 MHz,
[D6]DMSO): δ = 12.96 (s, 1 H), 8.03–8.00 (dd, J = 1.15 Hz, 7.77 Hz, 1
H), 7.95–7.93 (d, J = 7.8 Hz, 1 H), 7.82–7.78 (t, J = 7.44 Hz, 1 H),
7.67–7.63 (t, J = 7.80 Hz, 1 H), 7.53–7.51 (m, 4 H), 7.47–7.26 (m, 8
H) ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 148.8, 141.5, 132.6,
130.3, 130.0, 129.0, 128.0, 124.5, 124.0 ppm. IR: ν = 2964, 1583,
˜
1523, 1480, 1415, 1302, 1071 cm–1. ESI-MS (m/z) 364 [M + Na]+.
2-(2-Methoxyphenyl)-4,5-diphenyl-1H-imidazole (3g):[38] Yield
1
112.60 mg (69 %); white solid; m.p. 223–225 °C. H NMR (400 MHz,
[D6]DMSO): δ = 11.90 (s, 1 H), 8.10–8.08 (dd, J = 1.57 Hz, 7.42 Hz, 1
H), 7.58–7.56 (d, J = 7.65 Hz, 2 H), 7.49–7.47 (m, 2 H), 7.42–7.41 (t,
J = 7.20 Hz, 2 H), 7.39–7.36 (m, 2 H), 7.31–7.28 (t, J = 7.20 Hz, 2 H),
7.23–7.20 (m, 1 H), 7.18–7.16 (d, J = 8.10 Hz, 1 H), 7.09–7.06 (t, J =
7.42 Hz, 1 H), 3.93 (s, 1 H) ppm. 13C NMR (100 MHz, [D6]DMSO): δ =
156.9,144.1, 137.3, 136.2, 132.2, 130.7, 129.7, 129.5, 129.4, 129.0,
General Procedure for the Synthesis of 2,4,5-Trisubstituted
Imidazoles: A mixture of internal alkyne (0.5 mmol), I2 (1.5 equiv.)
and DMSO (1 mL) was reacted for 1 h at 130 °C. Thereafter, aldehyde
(0.5 mmol), ammonium acetate (10 equiv.) and EtOH (2 mL) was
added to the mixture and heated at 100 °C for 2 h. After cooling, a
solution of 1 % Na2S2O3 was added dropwise to the reaction mix-
ture to form a precipitate which was filtered and dried. The crude
product was recrystallized with ethanol to afford the desired prod-
uct 3.
2,4,5-Triphenyl-1H-imidazole (3a):[21,38] Yield 134.84 mg (90 %);
white solid; m.p. 270–272 °C. 1H NMR (400 MHz, [D6]DMSO): δ =
12.66 (s, 1 H), 8.09–8.07 (d, J = 7.6 Hz, 2 H), 7.53–7.52 (m, 4 H), 7.49–
7–45 (m, 3 H), 7.38–7.35 (m, 6 H) ppm. 13C NMR (100 MHz,
[D6]DMSO): δ = 146.0, 137.6, 135.7, 131.6, 130.9, 129.14, 129.1,
128.5,128.4, 128.0, 127.3,121.5, 119.8, 112.5, 56.5 ppm. IR: ν = 3196,
˜
3061, 2836, 1582, 1466, 1246, 1097 cm–1. ESI-MS (m/z) 327 [M +
H]+.
2-(2-Fluorophenyl)-4,5-diphenyl-1H-imidazole (3h):[42] Yield
114.74 mg (73 %); white solid; m.p. 268–272 °C. H NMR (400 MHz,
[D6]DMSO): δ = 12.55 (s, 1 H), 8.04–8.01 (td, J = 1.70 Hz, 1.40 Hz,
2.26 Hz, 1 H), 7.58–7.49 (m, 4 H), 7.49–7.45 (m, 1 H), 7.44–7.18 (m,
8 H), 7.53–7.51 (m, 4 H), 7.47–7.26 (m, 8 H) ppm. 13C NMR (100 MHz,
1
[D6]DMSO): δ = 160.6, 158.1, 141.3 (d, J
= 2 Hz), 137.8, 135.5,
C,F
131.4, 130.8 (d, J C,F = 8.1 Hz), 130.10 (d, J C,F = 2.9 Hz), 128.9, 125.1
(d, J
= 4.6 Hz), 119.1 (d, J
˜
= 11.5 Hz), 116.6 (d, J
= 20.6 Hz)
C,F
C,F
C,F
ppm. IR: ν = 3036, 1578, 1480, 1221, 1099, 701 cm–1. ESI-MS (m/z)
315 [M + H]+.
128.9, 128.71, 128.7, 128.2, 127.6, 127.0, 125.7 ppm. IR: ν = 3757,
˜
3037, 1586, 1461, 1484, 1126 cm–1. ESI-MS (m/z) 297 [M + H]+.
2-(3-Nitrophenyl)-4,5-diphenyl-1H-imidazole (3i):[39,40] Yield
2-(4-Bromophenyl)-4,5-diphenyl-1H-imidazole (3b):[39,40] Yield 122.89 mg (72 %); yellow solid; m.p. 268–272 °C. 1H NMR (400 MHz,
1
178.25 mg (95 %); white solid; m.p. 254–256 °C. H NMR (400 MHz,
[D6]DMSO): δ = 12.78 (s, 1 H), 8.07–8.03 (d, J = 8.5 Hz, 2 H), 7.71–
7.68 (d, J = 8.7 Hz, 2 H), 7.57–7–51 (m, 4 H), 7.48–7.44 (m, 2 H),
[D6]DMSO): δ = 13.10 (s, 1 H), 8.97 (s, 1 H), 8.54–8.52 (d, J = 7.70 Hz,
1 H), 8.24–8.22 (d, J = 7.87 Hz, 1 H), 7.82–7.78 (t, J = 8.04 Hz, 16.0 Hz,
1 H), 7.57–7.56 (m, 4 H), 7.41 (m, 6 H) ppm. 13C NMR (100 MHz,
Eur. J. Org. Chem. 0000, 0–0
www.eurjoc.org
5
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
[D6]DMSO): δ = 148.8, 143.8, 132.3, 131.6, 130.8, 128.9, 128.3, 127.9,
2641, 1599, 1478, 1442, 1070 cm–1. HRMS (ESI): cald. for
C21H14N2ClBr 409.0107, found 409.0114.
123.0, 119.9 ppm. IR: ν = 2738, 1580, 1518, 1476, 1415, 1344, 1248,
˜
1069 cm–1. ESI-MS (m/z) 342 [M + H]+.
2,5-Bis(4-chlorophenyl)-4-phenyl)-4-phenyl-1H-imidazole (3t)
(See the Supporting Information):[46] Yield 124.19 mg (68 %);
white solid; m.p. 245–249 °C. 1H NMR (400 MHz, [D6]DMSO): δ =
12.83 (s, 1 H), 8.12–8.10 (d, J = 8.47 Hz, 2 H), 7.57–7.38 (m, 11 H)
ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 145.1, 138.4, 136.5, 134.3,
133.4, 132.8, 131.6, 131.2, 130.4, 129.5, 129.3, 129.0, 128.8, 127.7,
2-(2-Naphthyl)-4,5-diphenyl-1H-imidazole
(3j):[43]
Yield
1
147.22 mg (85 %); white solid; m.p. 274–276 °C. H NMR (400 MHz,
[D6]DMSO): δ = 12.87 (s, 1 H), 8.64 (s, 1 H), 8.29–8.27 (d, J = 8.84 Hz,
1 H), 8.04–7.95 (m, 3 H), 7.60–7.53 (m, 6 H), 7.43–7.39 (m, 6 H) ppm.
13C NMR (100 MHz, [D6]DMSO): δ = 146.0, 133.5, 133.2, 128.9,128.7,
127.4 ppm. IR: ν = 2114, 1602, 1577, 1443, 1391, 1323, 773 cm–1
HRMS (ESI): calcd. for C21H15N2Cl2 365.0612, found 365.0619.
.
128.6, 128.3, 128.2, 127.2, 126.8, 124.2, 124.0 ppm. IR: ν = 2738,
˜
˜
1580, 1518, 1476, 1415, 1344, 1248, 1069 cm–1. ESI-MS (m/z) 347 [M
+ H]+.
2-Cyclohexyl-4,5-diphenyl-1H-imidazole (3k):[38] Yield 27.2 mg
Acknowledgments
(18 %); white solid; recrystallization solvent: ethyl acetate; m.p. 240–
1
We are grateful to the National Research Foundation (NRF) of
241 °C. H NMR (400 MHz, [D6]DMSO): δ = 11.91 (s, 1 H), 7.49–7.47
(d, J = 7.62 Hz, 2 H), 7.42–7.37 (m, 4 H), 7.32–7.24 (m, 3 H), 7.19– South Africa for a postgraduate bursary (S. N.) and a Thuthuka
7.16 (m, 1 H), 2.74–2.69 (m, 1 H), 2.00–1.97 (m, 2 H), 1.82–1.80 (m,
2 H), 1.71–1.56 (m, 3 H), 1.42–1.17 (m, 3 H) ppm. 13C NMR (100 MHz,
[D6]DMSO): δ = 152.9, 136.3, 135.5, 132.1, 129.0, 128.5, 128.3, 127.6,
research grant (V. J.). We thank Mr. Craig Grimmer for useful
advice regarding the NMR spectra.
127.5, 126.5, 126.2, 37.7, 32.0, 26.2, 26.1, 21.2 ppm. IR: ν = 3031,
˜
2925, 2850, 1593, 1446, 1366, 1183 cm–1. ESI-MS (m/z) 303.
Keywords: Alkynes · Iodine · Oxidation
3-(4,5-Diphenyl-1H-imidazol-2-yl)-1H-indole
(3m):[44]
Yield
91.0 mg (54 %); white solid; recrystallization solvent: ethanol; m.p.
215–220 °C. 1H NMR (400 MHz, [D6]DMSO): δ = 12.28 (s, 1 H), 11.38
(s, 1 H), 8.52–8.50 (d, J = 6.89 Hz, 1 H), 8.02 (s, 1 H), 7.68–7.66 (m, 2
H), 7.56–7.54 (m, 2 H), 7.46–7.44 (m, 3 H), 7.38–1.32 (m, 3 H), 7.25–
7.16 (m, 3 H) ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 144.2, 136.8,
136.5, 136.2, 132.1, 129.1, 128.6, 127.8, 127.4, 126.6, 126.2, 125.6,
[1] a) M. S. Chen, M. C. White, Science 2007, 318, 783–787; b) C. Liu, H.
Zhang, W. Shi, A. Lei, Chem. Rev. 2011, 111, 1780–1824; c) Y. Ashikari, T.
Nokami, J.-I. Yoshida, J. Am. Chem. Soc. 2011, 133, 11840–11843; d) A.
Shao, M. Gao, S. Chen, T. Wang, A. Lei, Chem. Sci. 2017, 8, 2175–2178.
[2] a) Z. Zhu, J. H. Espenson, J. Org. Chem. 1995, 60, 7728–7732; b) M. B.
Chaudhari, Y. Sutar, S. Malpathak, A. Hazra, B. Gnanaprakasam, Org. Lett.
2017, 19, 3628–3631.
[3] a) W. R. Gutekunst, P. S. Baran, Chem. Soc. Rev. 2011, 40, 1976–1991; b)
V. Jeena, R. S. Robinson, Org. Biomol. Chem. 2015, 13, 8958–8977.
[4] a) S. Mori, M. Takubo, T. Yanase, T. Maegawa, Y. Monguchi, H. Sajiki, Adv.
Synth. Catal. 2010, 352, 1630–1634; b) S. Chandrasekhar, N. K. Reddy,
V. P. Kumar, Tetrahedron Lett. 2010, 51, 3623–3625; c) N. Xu, D.-W. Gu, Y.-
S. Dong, F.-P. Yi, L. Cai, X.-Y. Wu, X.-X. Guo, Tetrahedron Lett. 2015, 56,
1517–1519.
[5] For selected examples on the synthesis of 1,2-diketones via internal alk-
yne oxidation see: a) Z. Wan, C. D. Jones, D. Mitchell, J. Y. Pu, T. Y. Zhang,
J. Org. Chem. 2006, 71, 826–828; b) M. Chen, Q. Zhao, D.-B. She, M.-Y.
Yang, H.-H. Hui, G.-S. Huang, J. Chem. Sci. 2008, 120, 347–351; c) W. Ren,
Y. Xia, S.-J. Ji, Y. Zhang, X. Wan, J. Zhao, Org. Lett. 2009, 11, 1841–1844;
d) M. Tingoli, M. Mazzella, B. Panunzi, A. Tuzi, Eur. J. Org. Chem. 2011,
399–404; e) C.-F. Xu, M. Xu, Y.-X. Jia, C.-Y. Li, Org. Lett. 2011, 13, 1556–
1559; f) A. Gao, F. Yang, J. Li, Y. Wu, Tetrahedron 2012, 68, 4950–4954.
[6] D. G. Lee, V. S. Chang, J. Org. Chem. 1979, 44, 2726–2730.
[7] Y. Miao, A. Dupé, C. Bruneau, C. Fischmeister, Eur. J. Org. Chem. 2014,
5071–5077.
[8] a) B. Rihter, S. SriHari, S. Hunter, J. Masnovi, J. Am. Chem. Soc. 1993, 115,
3918–3924.
[9] P. Li, F. H. Cheong, L. C. Chao, Y. H. Lin, I. D. Williams, J. Mol. Catal. A
1999, 145, 111–120.
[10] V. O. Rogatchov, V. D. Filimonov, M. S. Yusubov, Synthesis 2001, 1001–
1003.
[11] a) B. Cui, B. L. Zheng, K. He, Q. Y. Zheng, J. Nat. Prod. 2003, 66, 1101–
1103; b) F. Bellina, S. Cauteruccio, R. Rossi, Tetrahedron 2007, 63, 4571–
4624.
[12] a) S. Tsukamoto, T. Kawabata, H. Kato, T. Ohta, H. Rotinsulu, R. E. Mangin-
daan, R. W. Van Soest, K. Ukai, H. Kobayashi, M. Namikoshi, J. Nat. Prod.
2007, 70, 1658–1660; b) M. Roué, I. Dormart-Coulon, A. Ereskovsky, C.
Djediat, T. Perez, M. L. Bourguet-Kondracki, J. Nat. Prod. 2010, 73, 1277–
1282.
[13] S. R. Natarajan, J. B. Doherty, Curr. Top. Med. Chem. 2005, 5, 987–1003.
[14] A. K. Takle, M. J. Brown, S. Davies, D. K. Dean, G. Francis, A. Gaiba, A. W.
Hird, F. D. King, P. J. Lovell, A. Naylor, A. D. Reith, J. G. Steadman, M. D.
Wilson, Bioorg. Med. Chem. Lett. 2006, 16, 378–381.
124.3, 122.3, 122.0, 120.1, 112.1, 107.3 ppm. IR: ν = 3418, 2072,
˜
1600, 1493, 1452 cm–1. ESI-MS (m/z) 336 [M + H]+.
2-(2-Furanyl)-4,5-diphenyl-1H-imidzole (3n):[21] Yield 57.0 mg
(40 %); brown solid; m.p. 228–230 °C. 1H NMR (400 MHz, [D6]DMSO):
δ = 12.81 (s, 1 H), 7.81 (d, J = 1.06 Hz, 1 H), 7.54–7.51 (m, 4 H), 7.49–
7.42 (m, 2 H), 7.39–7.37 (m, 1 H), 7.33–7.29 (m, 2 H), 7.25–7.24 (m,
1 H), 6.99–6.98 (d, J = 3.16, 1 H) ppm. 13C NMR (100 MHz,
[D6]DMSO): δ = 146.2, 143.5, 139.1, 137.5, 135.4, 131.3, 129.1, 128.8,
128.7, 128.3, 128.0, 127.6, 127.1, 112.3, 107.9 ppm. IR: ν = 2819,
˜
2722, 1600, 1483, 1071 cm–1. ESI-MS (m/z) 286 [M + H]+.
4,5-Bis(4-bromophenyl)-2-phenyl-1H-imidazole
(3q):
Yield
54.50 mg (60 %) (based on a 0.15 mmol scale); white solid; m.p.
210–214 °C. 1H NMR (400 MHz, [D6]DMSO): δ = 12.80 (s, 1 H), 8.09–
8.07 (d, J = 7.23 Hz, 2 H), 7.66–7.55 (m, 5 H), 7.53–7.46 (m, 6 H),
7.42–7.39 (m, 1 H) ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 146.6,
136.6, 132.1, 132.0, 130.5, 130.2, 129.2, 129.0, 128.6, 125.8, 121.3
ppm. IR: ν = 2322, 2094, 1639, 1482, 1073, 965, 828 cm–1. HRMS
˜
(ESI): calcd. for C21H14Br2N2 452.9602 found 452.9608.
5-(4-Chlorophenyl)-2,4-diphenyl-1H-imidazole (3r):[45] Yield
1
117.40 mg (72 %); white solid; m.p. 242–245 °C. H NMR (400 MHz,
[D6]DMSO): δ = 12.75 (s, 1 H), 8.11–8.09 (d, J = 7.72 Hz, 2 H), 7.57–
7.50 (m, 6 H), 7.48–7.38 (m, 6 H) ppm. 13C NMR (100 MHz,
[D6]DMSO): δ = 146.8, 146.6, 138.7, 136.7, 135.9, 135.0, 133.2, 131.9,
131.8, 131.2, 131.1,131.0, 130.8, 129.8, 129.7, 129.52, 129.50, 129.3,
129.28, 129.23, 129.0, 128.2, 127.9, 127.7, 126.2, 126.18 ppm. IR: ν =
˜
3043, 1583, 1483, 1462, 1404, 1092, 767 cm–1. HRMS (ESI): cald. for
C
21H15N2Cl [M + H]+ 331.1002, found 331.1009.
2-(4-Bromophenyl)-5-(4-Chlorophenyl)-4-phenyl-1H-imidazole
(3s):[46] Yield 147.50 mg (72 %); white solid; m.p. 252–254 °C. 1H
NMR (400 MHz, [D6]DMSO): δ = 12.84 (s, 1 H), 8.05–8.03 (d, J =
8.65 Hz, 2 H), 7.71–7.68 (d, J = 8.68 Hz, 2 H), 7.56–7.52 (t, J = 8.55 Hz,
4 H), 7.42 (m, 5 H) ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 145.7,
[15] T. F. Gallagher, S. M. Fier-Thompson, R. S. Garigipati, M. E. Sorenson, J. M.
Smietana, D. Lee, D. E. Bender, J. C. Lee, J. T. Laydon, D. E. Griswold, M. C.
132.7, 130.3, 129.9, 129.5, 129.2, 128.1, 126.3, 122.5 ppm. IR: ν =
˜
Eur. J. Org. Chem. 0000, 0–0
www.eurjoc.org
6
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Chabot-Fletcher, J. J. Breton, J. L. Adams, Bioorg. Med. Chem. Lett. 1995,
5, 1171–1176.
[16] M. Yar, M. Bajda, S. Shahzad, N. Ullah, M. A. Gilani, M. Ashraf, A. Rauf, A.
Shaukat, Bioorg. Chem. 2015, 58, 65–71.
[31] a) S. Balalaie, A. Arabanian, Green Chem. 2000, 2, 274–276; b) E. Chau-
veau, C. Marestin, F. Schiets, R. Mercier, Green Chem. 2010, 12, 1018–
1022; c) J.-F. Zhou, G.-X. Gong, X.-J. Sun, Y.-L. Zhu, Synth. Commun. 2010,
40, 1134–1141.
[17] a) A. P. Kulkarni, C. J. Tonzola, A. Babel, S. A. Jenekhe, Chem. Mater. 2004,
16, 4556–4573; b) Z. Wang, P. Lu, S. Chen, Z. Gao, F. Shen, W. Zhang, Y.
Xu, H. S. Kwok, Y. Ma, J. Mater. Chem. 2011, 21, 5451–5456.
[18] I. Satoru, Chem. Abstr. 1989, 111, 214482.
[19] Selected examples include: a) N. Habersaat, R. Fröhlich, E.-U. Würthwein,
Eur. J. Org. Chem. 2004, 2567–2581; b) S. S. Boominathan, C.-Y. Chen, P.-
J. Huang, R.-J. Hou, J.-J. Wang, New J. Chem. 2015, 39, 6914–6918; c) N.
Rani, A. Sharma, R. Singh, Mini-Rev. Org. Chem. 2015, 12, 34–65; d) J. B.
Bharate, S. Abbat, R. Sharma, P. V. Bharatam, R. A. Vishwakarma, S. B.
Bharate, Org. Biomol. Chem. 2015, 13, 5235–5242.
[32] a) X. C. Wang, H. P. Gong, Z. J. Quan, L. Li, H. L. Ye, Chin. Chem. Lett.
2009, 20, 44–47; b) L.-M. Wang, Y.-H. Wang, H. Tian, Y.-F. Yao, J.-H. Shao,
B. Liu, J. Fluorine Chem. 2006, 127, 1570–1573.
[33] Y. Miao, A. Dupé, C. Bruneau, C. Fischmeister, Eur. J. Org. Chem. 2014,
5071–5077.
[34] a) M. Kidwai, P. Mothsra, V. Bansal, R. Goyal, Monatsh. Chem. 2006, 137,
1189–1194; b) M. Kidwai, P. Mothsra, V. Bansal, R. K. Somvanshi, A. S.
Ethayathulla, S. Dey, T. P. Singh, J. Mol. Catal. A 2007, 265, 177–182.
[35] V. Estévez, M. Villacampa, J. C. Menéndez, Chem. Commun. 2013, 49,
591–593.
[20] a) A. R. Karimi, Z. Alimohammadi, M. M. Amimi, Mol. Diversity 2010, 14,
635–641; b) A. Teimouri, A. N. Chermahini, J. Mol. Catal. A 2011, 346, 39–
45; c) K. Ramesh, S. N. Murthy, K. Karnakar, Y. V. Nageswar, K. Vijay-
lakshmi, B. L. A. Devi, R. B. Prasad, Tetrahedron Lett. 2012, 53, 1126–1129;
d) A. Maleki, H. Movahed, R. Paydar, RSC Adv. 2016, 6, 13657–13665.
[21] C.-Y. Chen, W.-P. Hu, P.-C. Yan, G. C. Senadi, J.-J. Wang, Org. Lett. 2013, 15,
6116–6119.
[36] a) L. Z. Yuan, A. Hamze, M. Alami, O. Provot, Synthesis 2017, 49, 504–525;
b) K. J. Tamuli, M. Bordoloi, ChemistrySelect 2018, 3, 7513–7517; c) G.
Kour, M. Gupta, B. Vishwanathan, K. Thirunavukkarasu, Dalton Trans.
2015, 44, 14975–14990; d) J. Safari, Z. Zarnegar, Ultrason. Sonochem.
2013, 20, 740–746.
[37] a) S. Jurić, B. Denegri, O. Kronja, J. Org. Chem. 2010, 75, 3851–3854.
[38] K. Bahrami, M. M. Khodei, A. Nejati, Monatsh. Chem. 2011, 142, 159–162.
[39] A. Hariharasubramanian, Y. D. Ravichandran, RSC Adv. 2014, 4, 54740–
54746.
[22] a) H. Togo, S. Iida, Synlett 2006, 14, 2159–2175; b) Y.-M. Ren, C. Cai, R.-C.
Yang, RSC Adv. 2013, 3, 7182–7204.
[23] a) W. W. Epstein, F. W. Sweat, Chem. Rev. 1967, 67, 247–260; b) A. J.
Mancuso, D. Swern, Synthesis 1981, 165–185.
[40] A. Shaabani, A. Maleki, A. Behnam, Synth. Commun. 2008, 39, 102–110.
[41] S. Goswami, R. Chakraborty, Eur. J. Chem. 2011, 2, 410–415.
[42] T. S. Chundawat, N. Sharma, P. Kumari, S. Bhagat, Synlett 2016, 27, 404–
408.
[43] J. Safari, S. D. Khalili, S. H. Banitaba, Synth. Commun. 2011, 41, 2359–
2373.
[44] S. Agarwal, M. Kidwai, R. Paddar, M. Nath, ChemistrySelect 2017, 2,
10360–10364.
[45] U. K. Das, L. J. Shimon, D. Milstein, Chem. Commun. 2017, 53, 13133–
13136.
[24] E. Jones-Mensah, M. Karki, J. Magolan, Synthesis 2016, 48, 1421–1436.
[25] K. Omura, A. K. Sharma, D. Swern, J. Org. Chem. 1976, 41, 957–962.
[26] K. E. Pfitzner, J. G. Moffatt, J. Am. Chem. Soc. 1963, 85, 3027–3028.
[27] E. J. Corey, M. Chaykovsky, J. Am. Chem. Soc. 1962, 84, 867–868.
[28] A. Monga, S. Bagchi, A. Sharma, New J. Chem. 2018, 42, 1551–1576.
[29] a) G. V. Sharma, Y. Jyothi, P. S. Lakshmi, Synth. Commun. 2006, 36, 2991–
3000; b) L. Nagarapu, S. Apuri, S. Kantevari, J. Mol. Catal. A 2007, 266,
104–108.
[30] a) C. Yu, M. Lei, W. Su, Y. Xie, Synth. Commun. 2007, 37, 3301–3309; b)
M. H. Heravi, F. Derikvand, F. F. Bamoharram, J. Mol. Catal. A 2007, 263,
112–114; c) T. S. Chundawant, N. Sharma, P. Kumari, S. Bhagat, Synlett
2016, 27, 404–408.
[46] J. Jayram, V. Jeena, Green Chem. 2017, 19, 5841–5845.
Received: October 23, 2018
Eur. J. Org. Chem. 0000, 0–0
www.eurjoc.org
7
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Imidazole Synthesis
S. Naidoo, V. Jeena* .......................... 1–8
One-Pot, Two-Step Metal and Acid-
Free Synthesis of Trisubstituted Im-
idazole Derivatives via Oxidation of
Internal Alkynes Using an Iodine/
DMSO System
A one-pot, two-step, simple, efficient system, has been reported. This metal
and eco-friendly oxidation of internal and acid-free reaction proceeded
alkynes as a key step towards the syn- smoothly to furnish a variety of substi-
thesis of 2,4,5-trisubstituted imidaz- tuted imidazoles in moderate to excel-
oles, using an inexpensive I2/DMSO lent yields.
DOI: 10.1002/ejoc.201801584
Eur. J. Org. Chem. 0000, 0–0
www.eurjoc.org
8
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim