Acid-catalyzed synthesis of imidazole derivatives via N-phenylbenzimidamides and sulfoxonium ylides cyclization

Article abstract of DOI:10.1016/j.tet.2019.04.004

A straightforward method to synthesize imidazole derivatives from amidines and sulfoxonium ylides catalyzed by acids is reported in this study. Specifically, catalyzed by trifluoroacetic acid in DCE solvents can improve synthesis efficiency under metal-fr

Full text of DOI:10.1016/j.tet.2019.04.004

Accepted Manuscript
Acid-catalyzed synthesis of imidazole derivatives via N-phenylbenzimidamides and
sulfoxonium ylides cyclization
Yuan Tian, Mingda Qin, Xueying Yang, Xueguo Zhang, Yafeng Liu, Xin Guo, Baohua
Chen
PII:
S0040-4020(19)30394-1
https://doi.org/10.1016/j.tet.2019.04.004
TET 30249
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 24 January 2019
Revised Date: 26 March 2019
Accepted Date: 1 April 2019
Please cite this article as: Tian Y, Qin M, Yang X, Zhang X, Liu Y, Guo X, Chen B, Acid-catalyzed
synthesis of imidazole derivatives via N-phenylbenzimidamides and sulfoxonium ylides cyclization,
Tetrahedron (2019), doi: https://doi.org/10.1016/j.tet.2019.04.004.
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ACCEPTED MANUSCRIPT

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Acid-catalysed synthesis of imidazole derivatives via
N-phenylbenzimidamides and sulfoxonium ylides
cyclization
a Yuan Tian, a Mingda Qin, a Xueying Yang, a Xueguo Zhang, a Yafeng Liu,
Xin Guo* a,b, Baohua Chen* a,c
a.State Key Laboratory of Applied Organic Chemistry, Key laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu
Province, Department of Chemistry,
Lanzhou University, Lanzhou, Gansu, China. E-mail: chbh@lzu.edu.cn
b. School of Chemistry and Chemical Engineering, North Minzu University, Yinchuan 750021, P.R.China.
c. Zhongwei High-Tech Institute of Lanzhou University, Zhongwei, Ningxia 755500, China
ABSTRACT
A straightforward method to synthesize imidazole derivatives from amidines and sulfoxonium ylides catalyzed by
acids is reported in this study. Specifically, catalysed by trifluoroacetic acid in DCE solvents can improve synthesis
efficiency under metal-free conditions. A series of imidazole scaffolds were produced in good to excellent yields.
Keywords:
Amidines
Sulfoxonium ylides
N-phenylbenzimidamides
Mild conditions Environment- friendly
1. Introduction
The imidazole ring represents an important class of heterocycles, which have been widely applied in
natural products, biological fields and pharmaceutical industries.1 As a privileged structural motif, imidazole
derivatives possess many meaningful biological properties, such as anti-plasmodium,2 anti-
inflammatory,3 antifungal,4 antibacterial5 and antitumoral6 ,among them, losartan (antihypertension), etomidate
(hypnotic agent) and
flumazenil (benzodiazepine antagonist) are
a
few examples of
N-aylimidazoles-containing drugs7a, which have been widely explored and utilized. Moreover, with the
continuous advancement of the chemical industry, imidazole derivatives have been exploited as precursors of
ligands in synthetic organic chemistry.7b-c, 8 Traditionally, many chemists had used a wide variety of transition
metal catalysed direct C-N formation reactions.9 Although effective as they were, most of them needed
complex reductants or suffered from some other disadvantages, such as a required use of non-ideal solvents
and poor functional group tolerance.10
Previously, our team worked to synthesize multi-substituted imidazoles efficiently through
metal-catalysed oxidation processes. For example, we formerly reported iron(III)-catalyzed synthesis of
1,2,4-trisubstituted imidazoles through the reactions of amidines, nitromethanes and aldehydes.11 The latest
synthetic multi-substituted imidazole methods have been published by our group in which amidines and
ketones were used to synthesize multi-substituted imidazoles via a [3+2] cycloaddition reaction co-catalyzed
by copper and zinc or I2 and zinc.12 For other synthetic methods of imidazoles using amidines, the Sachin’s

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Scheme 1. Strategies or the synthesis of imidazoles
group reported copper and oxygen co-catalyzed simultaneous activation of C-H and N-H bonds: a three-
component one-pot cascade synthesis of multisubstituted imidazoles. Also the Luc’s group reported
copper-catalyzed oxidative deamination of terminal alkynes by amidines: synthesis of 1,2,4-trisubstituted
imidazoles13. Akio’s group also reported a method of metal-free synthesis of imidazole some years ago. Such
as development of imino λ3 iodanes with improved reactivity for metal free [2+2+1] cycloaddition type
reactions14. These strategies were shown in Scheme 1. Although some achievements were made, the
reactions required precious metals or metal sails and some other strict conditions. Moreover, the operations
of these reactions were quite complicated. Encouraged by previous works, we have focused on a more direct
method for synthesizing multi-substituted imidazoles in the absence of metals and ligands under mild
conditions.
Therefore, we came up with a simple and economical method of synthesizing multi-substituted
imidazoles. We found a new substance called sulfoxonium ylide, which has a strong reactivity and can couple
a partner to deliver a carbene.15 Moreover, it was often used as a substrate, and would not require a critical
condition. And we employed a Brønsted acid-catalysed strategy to construct the polycyclic heterocycles,
among them, [3 + 2] cycloaddition proved to be one of the most efficient approaches, which could be used to
construct five-membered heterocycles16a. This strategy was applied to our reaction and highlighted some
advantages. The protocol is operationally simple, avoiding the use of toxic and scarce precious metal
catalysts16b. And this method is economical and environmentally friendly, and thus represents a novel and
efficient method for the construction of imidazoles.
2. Results and discussion
With reference to the previous works, our preliminary study began with 1 equiv of N-phenylbenzamidine
(1a) and 2 equiv of sulfoxonium ylide (2a) as the model substrates in solvents at 110 oC for 12 h (Table 1,). In
this reaction, the DCE was used as the best solvent among DMF, toluene, 1,4-dioxane and DCM. And our
desired product called 1,2,4-triphenyl imidazole (3aa) was obtained in 32% yield (Table 1, entry 5). When

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Table 1.Optimization of the Reaction Conditions a
Yield of
3aab %
Solvent
DMF
Entry
Catalyst
1
2
-
-
-
-
-
nrc
15
-
Toluene
3
1,4-dioxane
DCM
21
4
trace
32
5
DCE
6d
7e
8
-
DCE
23
-
DCE
34
Na2CO3
NaOAc
DCE
trace
33
9
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
10
11
12
13
14
15
16
17f
18g
HOAc
41
HCOOH
PivOH
57
45
CF3COOH
CF3SO3H
CCl3COOH
PhCOOH
CF3COOH
CF3COOH
83
81
53
50
78
27
aReaction conditions:1a (0.1 mmol), 2a (0.2 mmol), catalyst (50 mol%) in solvent
(2 mL) at heat for 12 h. b Isolated yield. c nr=no reaction. d 100 oC. e 120 oC. f
catalyst (20 mol%ꢀ. g catalyst (100 mol%).
o
the temperature was raised to 120 C, there was only a small increase in yield (Table 1, entry 7). So we
finally chose 110 oC as the best reaction temperature. Later we used bases and acids (50 mol%) as catalysts
respectively, and found that the catalytic performance of the base was worse than that of the acid in this
reaction. After employing trifluoracetic acid as the catalyst, we found that the yield could be satisfactorily
increase to 83% (Table 1, entry 13). Also trifluoromethanesulfonic acid was employed and could improve
the yield to 81% (Table 1, entry 14). However, under other acids, such as HOAc, HCOOH, PivOH,
CCl3COOH and PhCOOH, there seemed to appear less remarkable changes in the yields. Furthermore, we
tested the amount of acid separately with 20 mol% and 100 mol%, but still found that 50 mol% acids were
the best choice. Up to now, we have completed the qualification: 1a (1 equiv), 2a (2 equiv) and CF3COOH
(50 mol%) in DCE (2 ml) at 110 oC for 12 h.
Under the optimal condition, the substrates scope of amidine (1) and sulfoxonium ylide (2a) were
examined to establish the limitation of the reaction and the results are showed in Scheme 2. A variety of
1,2,4-trisubstituted imidazoles (3ba-3ja, 3ma-3ta) could be obtained by employing various amidines (1b-1t)
and sulfoxonium ylides (2a) , giving good yields ranging from 47% to 82%. Generally, compared to the

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electron-withdrawing groups (3ha-3ja,3qa-3ta), the electron-donating groups such as methyl-, methoxy-,
tert-butyl- could produce the corresponding products in better yields (3ba-3fa,3ma-3pa), which might be
Scheme 2.Substrate scope of amidine a
a Reaction conditions:1a (0.1 mmol), 2a (0.2 mmol), CF3COOH (50 mol%),
DCE (2 mL), 110 oC, 12 h. b Isolated yields. c nr=no reaction.
attributed to the electronic effects. More precisely, the electron-donating groups were able to increase the
activity of the amidines, which would be more conducive to the reaction. Specially, some substrates with the
meta substituent in N-phenylbenzimidamide (3ca) came up with low yields. Probably, due to the fact that the
electron-donating groups were detrimental to meta-activation. To our surprise, a substrate with an
ortro-chlorine (R2=2-Cl, 3qa) had an excellent yield up to 82%. Nevertheless, once the benzene ring was
replaced by a naphthalene ring, the yield would drop to 63% (3ga). We suspected that this might be due to
the steric hindrance effect of the naphthalene ring. To our disappointment, we failed to find the target
products when we changed benzene ring to pyridine ring (3ka) and n-butyl (3la) group. As to these

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phenomena, we suspected that the pyridine ring had a strong blunt effect not conducive to the reaction. We
also speculate that compared with the aliphatic substrate, the aromatic ring had conjugating effect beneficial
to the reaction.
On the other hand, the scope of sulfoxonium ylide was investigated as shown in Scheme 3. Generally,
benzoyl-substituted sulfoxonium ylides bear both electron-donating (3ab-3af) and a part of -withdrawing
groups (3ah,3ai,3ak), which all work well to deliver the desired products in moderate to good yields, such as
methyl-, ethyl-, methoxy-, ortro- or meta-chloro- and bromo-. But for para-chlorine (2g) and -fluorine (2j)
substrates of sulfoxonium ylides, the yield of the obtained products was only 57% and 45%. We suspected
that they might be caused by a strong electron withdrawing effect of fluorine and chlorine in the para
position. But for aliphatic substrates, they were still not conducive to the reaction, which was likely due to
aliphatic substrates of N- phenylbenzimidamide.
Scheme 3. Substrate scope of sulfoxonium ylide.
a Reaction conditions:1a (0.1 mmol), 2a (0.2 mmol), CF3COOH (50 mol%),
DCE (2 mL), 110 oC, 12 h. b Isolated yields. c nr=no reaction
To gain a further insight into the reaction, 2,2,6,6- tetramethyl- 1-piperidinyloxy (TEMPO, 2.0 equiv) was
added to the system, but the reaction provided merely a yield of 44% (Scheme 4, a). Then, we replaced the
TEMPO with 2,6-di-tert-butyl-4-methyl- phenol (BHT) in this system and to our surprise, the reaction still
provided a yield of 84% (Scheme 4, b). However, we discovered through experiments that TEMPO did not
capture any free radical intermediate. So we suggested that the reaction yield might have been reduced due
to the oxidative nature of TEMPO. So we rule out the possibility of a free radical reaction process. Later, we
replaced sulfoxonium ylide with acetophenone under the optimized condition and did not get any target
products (Scheme 4, c). Fortunately, the intermediate (E)-N-((Z)-2-(dimethyl(oxo)-l6-sulfanylidene) -1-

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phenylethylidene)-N'-phenylbenzimidamide B1 was detected by GC-MS analysis (m/ z = 374) after 6 h of
reaction.
Scheme 4. Control experiments
O
(d)
S
O
NH
O
N
N
N
S
N
+
6h
N
+
H
Standard condition
84%
B1
Scheme 5. Proposed mechanism
On the basis of the aforementioned information17 and our preliminary mechanistic results, a plausible
mechanism of coupling of 1a with 2a was proposed in Scheme 5. Initially, under acidic conditions,
hydrogen ions attacked the carbonyl oxygen atoms of the sulfoxonium ylide 2a, causing the carbonyl group
to have a positive charge to form intermediates A. At the same time, amidines are subjected to resonance
transformation to form intermediates 1aa. Then, the amino nitrogen atoms attacked the carbonyl carbon
atoms and then removed the hydronium ions to form
intermediates
B1.
At the
same
time,
intermediates B1 resonated to form intermediates B2. Next, the negatively charged carbon atoms of
intermediate B2 were combined with protons again to form intermediate C. In the intermediate C molecule,
the nitrogen atom which attached to the benzene ring attacked the same carbon atom, and the DMSO
molecule was removed to form intermediate D. Finally, the proton was removed from intermediate D via
electron transferring inside the intermediate D molecule to form the target product 3aa.

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3. Conclusion
In summary, an efficient acid-catalyzed method to synthesize multi-substituted imidazoles from the
amidines and sulfoxonium ylides was carried out. We used CF3COOH as the catalyst in the DCE, which
served as thesolvent in this reaction. The reaction tolerates a wide range of aromatic functional groups such as
alkyl-, methoxy-, fluoro-, chloro-, trifluoromethyl- and naphthalene rings, which afforded the imidazole
skeletons in good yields with high regioselectivity. Moreover, the reaction is economical, easy-to-operate and
environmentally friendly.
4.Experimental section
4.1 General
1
All reagents were commercially available and used as is without further purification. H NMR spectra
were recorded at 300 MHz in CDCl3 and 13C NMR spectra were recorded at 75 MHz in CDCl3 using TMS as
the internal standard. Melting points were determined on a microscopic apparatus..HRMS was performed
using an FT-ICRMS mass instrument and measured with electrospray ionization (ESI). Products were purified
by flash chromatography on 200-300 mesh silica gel. Unless otherwise noted, commercially reagents were
used without further purification.
4.2 General procedure for the synthesis of 1,2,4- triphenylimidazole (3a)
All the reactions were carried out in a reaction vessel (10 mL), N-phenylbenzamidine (1a, 0.1 mmol),
sulfoxonium ylides (2a,0.2 mmol), trifluoroacetate (50 mol%) and DCE (2 ml) were successfully mixed in the
flask using a magnetic stir bar and reacted at 110 oC for 12 h in the presence of air. Then the mixture was
removed from the oil bath and cooled to room temperature. The mixture was filtered and washed with ethyl
acetate (3×50 mL) and the crude product was obtained by concentrating under reduced pressure. Finally,
product 3a was isolated as a yellow oil by silica gel chromatography (petroleum ether/ethyl acetate = 10/1 as
the eluent).The remaining substituted imidazoles were prepared in a similar manner.
4.3Compound data of products 3aa
4.3.1. 1,2,4-triphenyl-1H-imidazole
ꢁ3aaꢀ
1
Compound 3aa was isolated as yellow oil (83% yield, 24.6 mg) H NMR (300 MHz, CDCl3) δ 7.27 (d, J =
7.3 Hz, 2H), 6.80 (d, J= 17.3 Hz, 7H), 6.69 – 6.55 (m, 7H). 13C NMR (75 MHz, CDCl3) δ 146.86 (s), 141.55
(s), 138.33 (s), 133.68 (s), 129.36(s),129.11(s),128.08 (s), 127.71 (s),128.08 (s), 126.88 (s), 125.70 (s)
124.92(s), 118.40 (s). This spectrum is in agreement with previously reported spectral data.12
4.3.2. 2,4-diphenyl-1-(o-tolyl)-1H-imidazole (3ba)
Compound 3ba was isolated as yellow oil (71% yield, 22.0 mg). 1H NMR (300 MHz, CDCl3) δ 7.82 (d, J =
7.3 Hz, 2H), 7.41– 7.26 (m, 5H), 7.24 – 7.13 (m, 8H), 1.90 (s, 3H).13C NMR (75MHz, CDCl3) δ 147.18
(s), 141.54 (s), 137.73 (s), 134.97 (s),133.88 (s), 131.22 (s), 130.41 (s), 129.08 (s), 128.52 (s), 128.17(s),
127.64 (s), 127.01 (s),124.91 (s), 118.45 (s), 17.46 (s). This spectrum is in agreement with previously reported
spectral data.13
4.3.3. 2,4-diphenyl-1-(m-tolyl)-1H-imidazole (3ca)
Compound 3ca was isolated as yellow oil (60% yield, 18.6 mg). 1H NMR (300 MHz, CDCl3) δ 7.82 (d, J
= 7.5 Hz, 2H), 7.45–7.29 (m, 6H), 7.22 – 7.11 (m, 6H), 7.04 (s, 1H), 2.28 (s, 3H).13C NMR (75MHz,
CDCl3) δ 141.63 (s), 139.70 (s), 138.49 (s),133.97 (s), 130.43 (s), 129.26 (s), 129.00 (s), 128.81 (s),
128.65(s), 128.45 (s), 128.21 (s),127.90 (s), 127.01 (s), 126.36 (s),125.09 (s), 123.10 (s), 118.67
(s), 21.36 (s). This spectrum is in agreement with previously reported spectral data.13
4.3.4. 2,4-diphenyl-1-(p-tolyl)-1H-imidazole (3da)
Compound 3da was isolated as yellow oil (80% yield, 24.7 mg). 1H NMR (300 MHz, CDCl3) δ
7.84 – 7.79 (m,2H), 7.42 –7.37 (m, 2H), 7.35 – 7.29 (m, 3H), 7.22 – 7.16 (m, 4H), 7.15 –7.04 (m, 4H), 2.32
(s, 3H).13C NMR (75 MHz, CDCl3) δ 146.94(s), 141.50 (s), 138.15 (s), 135.94 (s), 133.89 (s), 130.01
(s), 128.75 (s), 128.56 (s), 128.33 (s), 128.14 (s)ꢂ126.91 (s), 125.59 (s), 124.99 (s), 118.63 (s), 21.12 (s). This
spectrum is in agreement with previously reported spectral data.12

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4.3.5. 1-(4-methoxyphenyl)-2,4-diphenyl-1H-imidazole (3ea)
Compound 3ea was isolated as yellow oil (73% yield, 23.8 mg). 1H NMR (300 MHz, CDCl3) δ 7.81 (d, J =
7.4 Hz, 2H), 7.43–7.28 (m, 5H), 7.19 (dd, J = 6.2, 2.5 Hz, 4H), 7.11 (d, J = 8.8 Hz,2H), 6.83 (d, J = 8.8 Hz,
2H), 3.76 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 159.50 (s), 141.61 (s), 134.09 (s), 128.95 (s), 128.81 (s),
128.58 (s), 128.40 (s), 127.30 (s), 127.17 (s), 125.25 (s), 122.56 (s), 119.08 (s), 114.80 (s), 114.64 (s), 55.76
(s). This spectrum is in agreement with previously reported spectral data.12
4.3.6.1-(4-(tert-butyl)phenyl)-2,4-diphenyl-1H-imidazole (3fa)
Compound 3fa was isolated as yellow oil (74% yield, 26.1 mg). 1H NMR (300 MHz, CDCl3) δ 7.80 (dt, J =
8.2, 1.7 Hz, 2H), 7.40– 7.36 (m, 2H), 7.34 – 7.28 (m, 5H), 7.21 – 7.14 (m, 4H), 7.11 –7.06 (m, 2H), 1.26 (s,
9H).13C NMR (75 MHz, CDCl3) δ 151.30(s), 146.86 (s), 141.38 (s), 135.71 (s), 133.78 (s), 130.26
(s), 128.68 (s), 128.46 (s), 128.23 (s), 128.03 (s),126.81 (s), 126.21 (s), 126.03 (s),125.19 (s), 124.92 (s),
118.56 (s), 34.61 (s), 31.19 (s), 29.58 (s). HRMS (ESI) calcd for C25H24N2 (M+H)+ 353.2012, found 353.2013.
4.3.7. 1-(naphthalen-2-yl)-2,4-diphenyl-1H-imidazole (3ga)
1
Compound 3ga was isolated as a white solid (63% yield, 21.8 mg). H NMR (300 MHz, CDCl3) δ 7.94 –
7.81 (m, 6H), 7.59 – 7.53 (m, 3H), 7.51 – 7.48 (m, 2H), 7.42 (t, J = 7.5 Hz, 2H), 7.31– 7.23 (m, 5H). 13C NMR
(75 MHz, CDCl3) δ 147.33 (s), 142.01 (s), 136.19 (s), 134.06 (s), 133.53 (s), 132.71 (s), 130.53
(s), 129.71 (s),129.04 (s), 128.85 (s), 128.72 (s), 128.49 (s), 128.25(s), 128.12 (s), 127.39 (s), 127.27 (s),
127.13 (s),125.30 (s), 124.37 (s), 124.04 (s), 119.03 (s). HRMS (ESI) calcd for C25H18N2 (M+H)+ 347.1543,
found 347.1544.
4.3.8. 1-(4-fluorophenyl)-2,4-diphenyl-1H-imidazole (3ha)
Compound 3ha was isolated as yellow oil (72% yield, 22.6 mg). 1H NMR (300 MHz, CDCl3) δ 7.83 (dd, J =
7.2, 0.8 Hz, 2H), 7.36 (ddd, J = 11.4, 8.0, 6.0 Hz, 5H), 7.26 – 7.15 (m, 6H), 7.04 (t, J = 8.2 Hz, 2H).13C NMR
(75 MHz, CDCl3) δ 147.11 (s), 141.80 (s), 133.68 (s), 130.88 - 130.06 (d, J = 61.5 Hz), 128.77
(s), 128.60 (s), 128.57 (s), 128.28 (s), 127.67-127.56 (d, J = 8.3 Hz), 127.55 (s),127.08 (s), 125.04 (s), 118.48
(s), 116.61 -116.31 (d, J=22.5 Hz). HRMS (ESI) calcd for C21H15N2F (M+H)+ 315.1292, found 315.1294.
4.3.9. 1-(4-chlorophenyl)-2,4-diphenyl-1H-imidazole (3ia)
Compound 3ia was isolated as yellow oil (66% yield, 21.8 mg). 1H NMR (300 MHz, CDCl3) δ 7.84 –
7.78 (m, 2H), 7.40 – 7.27 (m, 7H), 7.25 – 7.16 (m, 4H), 7.15 – 7.08 (m, 2H).13C NMR (75 MHz, CDCl3) δ
146.80 (s), 141.76 (s), 136.71 (s), 133.78 (s), 133.36 (s), 129.74 (s), 129.47 (s), 128.61 (s), 128.40 (s), 128.12
(s), 126.93 (s), 126.78 (s),124.84 (s), 117.97 (s). This spectrum is in agreement with previously reported
spectral data.12
4.3.10. 1-(2-chlorophenyl)-2,4-diphenyl-1H-imidazole (3ja)
Compound 3ja was isolated as a light yellow solid (65% yield, 21.4 mg). 1H NMR (300 MHz, CDCl3)δ
7.88 – 7.82 (m, 2H),7.45 (dd, J = 4.8, 4.0 Hz, 1H), 7.35 (ddt, J = 7.8, 6.3, 2.8 Hz, 6H), 7.28 – 7.14 (m,
6H).13C NMR (75 MHz, CDCl3) δ 147.24 (s), 135.87 (s), 133.29 (s), 131.31 (s), 130.22 (s), 129.75 (s),
128.95 (s),128.13 (s), 127.78 (s), 127.60 (s), 127.35 (s), 126.58 (s), 124.63 (s), 118.03 (s). This
spectrum is in agreement with previously reported spectral data.13
4.3.11. 1,4-diphenyl-2-(o-tolyl)-1H-imidazole (3ma)
Compound 3ma was isolated as yellow oil (79% yield, 24.5 mg). 1H NMR (300 MHz, CDCl3) δ 7.92 –
7.85 (m, 2H), 7.50 (s, 1H), 7.38 (t, J = 7.7 Hz, 2H), 7.31 – 7.19 (m, 6H), 7.15 – 7.06 (m, 4H), 2.10 (s,
3H).13C NMR (75 MHz, CDCl3) δ 146.87 (s), 141.30 (s), 137.76 (s), 133.74 (s), 130.84 (s), 130.36
(s), 130.16 (s), 129.08 (s), 128.47 (s), 127.35 (s), 126.82 (s), 125.44 (s), 124.85 (s), 124.39 (s),
116.29 (s),19.84 (s). This spectrum is in agreement with previously reported spectral data.13
4.3.12. 1,4-diphenyl-2-(m-tolyl)-1H-imidazole (3na)
Compound 3na was isolated as yellow oil (75% yield, 23.2 mg). 1H NMR (300 MHz, CDCl3) δ 7.90 (dd,
J = 8.3, 1.2 Hz, 2H), 7.47 – 7.35 (m, 7H), 7.26 (ddd, J = 7.1, 5.2, 1.7 Hz, 3H), 7.12 –7.04 (m, 3H), 2.29 (s, 3H).
13C NMR (75 MHz, CDCl3) δ 147.13 (s), 141.56 (s), 138.45 (s), 137.97 (s), 133.80 (s), 130.05 (s),129.57
(s), 129.37 (s), 129.20 (s), 128.55 (s), 128.07 (s), 127.85 (s), 126.92 (s), 125.77 (s), 125.01 (s),
118.37 (s),21.31 (s). This spectrum is in agreement with previously reported spectral data.13
4.3.13. 1,4-diphenyl-2-(p-tolyl)-1H-imidazole (3oa)
Compound 3oa was isolated as yellow oil (72% yield, 22.3 mg). 1H NMR (300 MHz, CDCl3) δ 7.82 (d, J
= 7.3 Hz, 2H), 7.31 (ddd, J = 17.0, 10.8, 6.6 Hz, 8H), 7.19 (dt, J = 5.8, 2.7 Hz, 3H), 7.00 (d, J = 8.0 Hz, 2H),
2.24 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 141.44 (s), 138.47 (s), 138.29 (s),133.78 (s), 129.34 (s), 128.80 (s),
128.60 (s), 128.48 (s), 128.00 (s), 127.28 (s), 126.84 (s), 125.76 (s), 124.95 (s), 118.23 (s), 21.19 (s).

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This spectrum is in agreement with previously reported spectral data.13
4.3.14. 2-(4-methoxyphenyl)-1,4-diphenyl-1H-imidazole (3pa)
Compound 3pa was isolated as yellow oil (78% yield, 25.4 mg). 1H NMR (300 MHz, CDCl3) δ 7.84 –
7.78 (m, 2H), 7.38 – 7.26 (m, 7H), 7.23 – 7.15 (m, 4H), 6.75 – 6.68 (m, 2H), 3.70 (s, 3H).13C NMR (75 MHz,
CDCl3) δ 159.99 (s), 147.22 (s), 141.68 (s), 138.84 (s), 134.16 (s), 130.43 (s), 129.68 (s),128.80
(s), 128.30 (s), 127.14 (s), 126.10 (s), 125.25 (s), 123.11 (s), 118.35 (s), 113.88 (s),55.45 (s). This spectrum is
in agreement with previously reported spectral data.13
4.3.15. 2-(2-chlorophenyl)-1,4-diphenyl-1H-imidazole (3qa)
1
Compound 3qa was isolated as yellow oil (82% yield, 27.6 mg). H NMR (300 MHz, CDCl3) δ 7.85 –
7.81 (m, 2H), 7.51 – 7.46 (m, 2H), 7.37 – 7.29 (m, 2H), 7.28 – 7.17 (m, 7H), 7.12 –7.07 (m, 2H).13C NMR (75
MHz, CDCl3) δ 144.94 (s), 142.03 (s), 138.07 (s), 134.68 (s), 133.92 (s), 132.96 (s),130.87 (s), 130.72 (s),
129.90 (s), 129.42 (s), 128.85 (s), 127.96 (s), 127.29 (s), 126.98 (s), 125.29 (s), 124.80 (s), 117.19
(s). This spectrum is in agreement with previously reported spectral data.12
4.3.16. 2-(3-chlorophenyl)-1,4-diphenyl-1H-imidazole (3ra)
Compound 3ra was isolated as yellow oil (58% yield, 19.1 mg). 1H NMR (300 MHz, CDCl3) δ 7.82 (d, J
= 7.4 Hz, 2H), 7.51 (s, 1H), 7.42 – 7.31 (m, 6H), 7.25 – 7.17 (m, 6H).13C NMR (75 MHz, CDCl3) δ 141.98 (s),
138.16 (s), 134.27 (s), 133.62 (s), 132.01 (s), 129.65 (s), 129.34 (s), 128.83 (s), 128.65 (s), 128.54 (s), 128.49
(s), 127.17 (s), 126.66 (s), 125.87 (s), 125.06 (s), 118.91 (s). This spectrum is in agreement with
previously reported spectral data.13
4.3.17. 2-(4-chlorophenyl)-1,4-diphenyl-1H-imidazole (3sa)
Compound 3sa was isolated as yellow oil (65% yield, 20.5 mg). 1HNMR (300 MHz, CDCl3) δ 7.88 (d, J
= 7.4 Hz, 2H), 7.47–7.38 (m, 7H), 7.32 – 7.22 (m, 6H). 13C NMR (75 MHz, CDCl3) δ 145.85 (s), 138.29 (s),
134.53 (s), 129.98 (s), 129.65 (s), 128.83 (s), 128.65 (s),128.49 (s), 127.14 (s), 125.88 (s), 125.06
(s), 118.79 (s). This spectrum is in agreement with previously reported spectral data.13
4.3.18. 1,4-diphenyl-2-(4-(trifluoromethyl)phenyl)-1H-imidazole (3ta)
Compound 3ta was isolated as yellow oil (47% yield, 17.1 mg). 1H NMR (300 MHz, CDCl3) δ 7.81 (dd, J
= 8.2, 1.0 Hz, 2H), 7.48 (dd, J = 20.8, 8.5 Hz, 4H), 7.41 – 7.30 (m, 6H), 7.25 – 7.17 (m, 3H).13C NMR (75
MHz, CDCl3) δ 167.58 - 164.10 (d, J = 261.0 Hz), 145.24 (s), 142.08 (s), 138.01 (s), 130.77 (s), 129.64-128.68
(d, J = 72.0 Hz), 128.71 (s),127.15 (s), 125.77 (s), 125.11–124.95 (q, J = 12.0 Hz), 119.19 (s), 112.78 (s).This
spectrum is in agreement with previously reported spectral data.12
4.3.19. 1,2-diphenyl-4-(o-tolyl)-1H-imidazole (3ab)
Compound 3ab was isolated as yellow oil (75% yield, 23.2 mg). 1H NMR (300 MHz, CDCl3) δ 7.91 (d, J
= 7.1 Hz, 1H), 7.42-7.28 (m, 5H), 7.18 (ddd, J = 9.0, 6.3, 3.5 Hz, 9H), 2.49 (s, 3H). 13C NMR (75 MHz, CDCl3)
δ 145.99 (s), 140.99 (s), 138.49(s), 134.97 (s), 133.12 (s), 130.71 (s), 130.26 (s), 129.45 (s), 128.76 (s), 128.63
(s), 128.35 (s), 128.13 (s), 126.93 (s), 125.95 (s), 125.87 (s), 120.99 (s), 21.87 (s). This spectrum is in
agreement with previously reported spectral data.12
4.3.20. 1,2-diphenyl-4-(m-tolyl)-1H-imidazole (3ac)
Compound 3ac was isolated as yellow oil (76% yield, 23.6 mg). 1H NMR (300 MHz, CDCl3) δ 7.68 (s, 1H),
7.57 (d, J = 7.7 Hz, 1H), 7.39 – 7.32 (m, 3H), 7.29 (dd, J = 5.3, 1.7 Hz, 3H), 7.20-7.12 (m, 6H), 6.99 (d, J = 7.5
Hz, 1H), 2.31 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 146.88 (s), 141.76 (s), 138.44 (s), 138.15 (s), 133.68 (s),
130.30 (s), 129.42 (s), 128.79 (s), 128.45 (s), 128.39 (s), 128.16 (s), 128.10 (s), 127.77 (s), 125.78 (s), 125.74
(s), 122.09 (s), 118.47 (s), 21.48 (s). This spectrum is in agreement with previously reported spectral data.12
4.3.21. 1,2-diphenyl-4-(p-tolyl)-1H-imidazole (3ad)
Compound 3ad was isolated as yellow oil (72% yield, 22.3 mg). 1H NMR (300 MHz, CDCl3) δ 7.71 (d, J
= 8.0 Hz, 2H), 7.40-7.27 (m, 6H), 7.22 – 7.09 (m, 7H), 2.28 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 146.75 (s),
141.72 (s), 138.45 (s), 136.56 (s), 130.96 (s), 130.30 (s), 129.38 (s), 129.23 (s), 128.74 (s), 128.31 (s), 128.11
(s), 128.02 (s), 125.75 (s), 124.88 (s), 118.03 (s), 21.21 (s). This spectrum is in agreement with previously
reported spectral data.12
4.3.22. 4-(4-ethylphenyl)-1,2-diphenyl-1H-imidazole (3ae)
Compound 3ae was isolated as yellow oil (85% yield, 27.5 mg). 1H NMR (300 MHz, CDCl3) δ 7.80 (d, J
= 8.2 Hz, 2H), 7.46-7.34 (m, 6H), 7.28 – 7.19 (m, 7H), 2.66 (q, J = 7.6 Hz, 2H), 1.25 (t, J = 7.6 Hz, 3H).13C
NMR (75 MHz, CDCl3) δ 147.07 (s), 143.32 (s), 142.07 (s), 138.75 (s), 131.51 (s), 130.59 (s), 129.69 (s),

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129.07 (s), 128.64 (s), 128.43 (s), 128.35 (s), 126.06 (s), 125.30 (s), 118.37 (s), 28.91 (s), 15.84 (s).
HRMS (ESI) calcd for C23H20N2 (M+H)+ 325.1699, found 325.1698.
4.3.23. 4-(4-methoxyphenyl)-1,2-diphenyl-1H-imidazole (3af)
1
Compound 3af was isolated as yellow oil (91% yield, 29.6 mg). H NMR (300 MHz, CDCl3) δ 7.84 –
7.76 (m, 2H), 7.47 – 7.32 (m, 6H), 7.27 – 7.19 (m, 5H), 6.97 – 6.89 (m, 2H), 3.81 (s, 3H). 13C NMR (75
MHz, CDCl3) δ 159.08 (s), 146.99 (s), 141.81 (s), 138.76 (s), 129.69 (s), 129.03 (s),128.61 (s), 128.43 (s),
128.32 (s), 126.93 (s), 126.54 (s), 126.05 (s), 117.80 (s), 114.27 (s), 55.53 (s). This spectrum is in
agreement with previously reported spectral data.13
4.3.24. 4-(4-chlorophenyl)-1,2-diphenyl-1H-imidazole (3ag)
Compound 3ag was isolated as yellow oil (57% yield,18.8 mg). 1H NMR (300 MHz, CDCl ) δ 7.83 (d, J
= 8.5 Hz, 2H), 7.47-7.34 (m, 8H), 7.31 – 7.22 (m, 5H).13C NMR (75 MHz, CDCl3) δ 146.83 (s), 140.76 (s),
138.44 (s), 132.68 (s), 131.06 (s), 129.68 (s), 128.92 (s), 128.74 (s), 128.45 (s), 128.39 (s), 126.41
(s), 125.94 (s), 118.81 (s). This spectrum is in agreement with previously reported spectral data.12
4.3.25. 4-(3-chlorophenyl)-1,2-diphenyl-1H-imidazole (3ah)
Compound 3ah was isolated as yellow oil (87% yield,28.7 mg). 1H NMR (300 MHz, CDCl3) δ 7.88 (t, J =
1.8 Hz, 1H), 7.72 (d, J= 7.7 Hz, 1H), 7.40 (ddd, J = 7.0, 6.2, 2.0 Hz, 6H), 7.29 – 7.19 (m, 7H). 13C NMR
(75 MHz, CDCl3) δ 140.57 (s), 138.46 (s), 135.89 (s), 134.80 (s), 131.11 (s),130.21 (s), 130.05 (s), 129.73
(s), 128.98 (s), 128.82 (s), 128.54 (s), 128.45 (s), 127.11 (s), 126.00 (s), 125.28 (s), 123.24 (s).
This spectrum is in agreement with previously reported spectral data.13
4.3.26. 4-(4-fluorophenyl)-1,2-diphenyl-1H-imidazole (3ai)
1
Compound 3ai was isolated as yellow oil (45% yield,14.2 mg). H NMR (300 MHz, CDCl3) δ 7.89 –
7.82 (m, 2H), 7.47 – 7.37 (m, 6H), 7.26 (ddd, J = 6.9, 3.4, 1.2 Hz,5H), 7.09 (t, J = 8.6 Hz, 2H). 13C NMR (75
MHz, CDCl3) δ 163.80 - 160.55 (d, J=243.8 Hz), 147.09 (s), 140.90 (s), 138.42 (s), 130.18 (s), 130.12-130.08
(d, J=3.0 Hz), 129.56(s), 128.83 (s), 128.29 (s), 126.75-126.65 (d, J = 7.5 Hz), 125.87 (s), 118.21 (s),
115.67 - 115.39 (d, J = 21.0 Hz). This spectrum is in agreement with previously reported spectral data.12
4.3.27. 4-(4-bromophenyl)-1,2-diphenyl-1H-imidazole (3aj)
Compound 3aj was isolated as yellow oil (78% yield, 29.3 mg). 1H NMR (300 MHz, CDCl3) δ 7.77 –
7.72 (m, 2H), 7.52 – 7.47 (m, 2H), 7.45 – 7.35 (m, 6H), 7.29 – 7.18 (m, 5H). 13C NMR (75 MHz, CDCl3) δ
147.54 (s), 140.95 (s), 138.62 (s), 133.20 (s), 132.03 (s), 130.39 (s), 129.89 (s),129.13 (s), 128.96 (s), 128.67
(s), 128.60 (s), 126.95 (s), 126.14 (s), 121.01 (s), 119.08 (s). This spectrum is in agreement with previously
reported spectral data.12
Acknowledgments
We gratefully acknowledge, for funding this project, the National Natural Science Foundation of
China (Nos.21372102). And, Key Scientific Research Projects in 2017 at North Minzu University
(Grant No.2017KJ16).
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