Transition-metal-free three-component reaction: Additive controlled synthesis of sulfonylated imidazoles

Article abstract of DOI:10.1021/acs.joc.9b01818

Two efficient transition-metal-free highly regioselective pathways for constructing sulfonylated imidazoles via three-component reactions of amidines, ynals, and sodium sulfonates have been developed. The generations of different sulfonylated imidazoles w

Full text of DOI:10.1021/acs.joc.9b01818

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Note
Transition-Metal-Free Three-Component Reaction:
Additive Controlled Synthesis of Sulfonylated Imidazoles
Wei Liu, Yu Zhang, Jiaming He, Yue Yu, Jiajun Yuan, Xiaoyi Ye, Ziwu Zhang, Liang Xue, and Hua Cao
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01818 • Publication Date (Web): 03 Aug 2019
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Transition-Metal-Free Three-Component Reaction:
Additive Controlled Synthesis of Sulfonylated Imidazoles
Wei Liu, Yu Zhang, Jiaming He, Yue Yu,* Jiajun Yuan, Xiaoyi Ye, Ziwu Zhang,
Liang Xue and Hua Cao*
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School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University,
Zhongshan, 528458, P.R. of China
Email: yuyue@gdpu.edu.cn; caohua@gdpu.edu.cn
Ar
O
S R1
N
CHO
Ar
H
O
Ar
TBHP
MeCN
N
Ar2
AcOH
EtOH
N
Ar2
Ar1
O
+
+
S
N
R1 ONa
Ar2
1
O S O
NH
N
Ar1
Ar
R1
ABSTRACT: Two efficient transition-mental-free highly regioselective pathways for
constructing sulfonylated imidazoles via three-component reactions of amidines,
ynals and sodium sulfonates have been developed. The generations of different
sulfonylated imidazoles were simply controlled by additives. In addition, this method
features environmental friendliness, good functional group tolerance and high atom
economy, which makes it practical.
Imidazole ring is an important and highly polar five-membered aromatic heterocycle,
which was widely distributed in nature products, applied pharmaceuticals, materials
and other fields.1-3 Imidazole compounds have a wide range of pharmacological
activities such as antifungal, antitumor, anti-inflammatory and antibacterial. Therefore,
4
these compounds have received extensive concern from researchers. Selected
examples such as Olprinone, Trifenagrel and Alpidem. Classic method for synthesis
5
of imidazoles was Debus-Radziszewski reaction. To date, a large number of
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transition-mental-catalyzed approaches were applied to produce imidazole derivatives,
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such as iron catalyzed, copper catalyzed, zinc catalyzed, silver catalyzed, gold
catalyzed,10 palladium catalyzed,11 nanocatalyzed12 and so on. However, the
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formation of imidazole derivatives by metal-free was seldom reported. To enrich
these green synthesis methods, it is extremely important to develop metal-free
strategies for the synthesis of functionalized imidazoles, especially sulfonylated
derivatives,14 which are otherwise difficult to construct and can be used in the
15
synthesis of new nitrogen/sulfon-fused molecules. Due to their unique chemical and
biological properties, sulfonylated heterocycles16,17 have emerged over the past few
years as important synthetic targets and central pharmacophore in a large number of
1
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biologically active medicinal agents. In particular, sulfonylated imidazoles were
reported to show good activities against Gram-positives bacteria and Gram-negative
bacteria that have the potential to overcome the increasing antibiotic resistance.19
Recently, our group has reported various Ag-catalyzed strategies for the
2
0
synthesis of functionalized imidazoles (Scheme 1a). It was found that amidines and
ynals could go through an intramolecular dehydration to form the imine intermediate,
which was activated by the silver-complex to react with nucleophiles such as alcohol,
acid, amine and etc, giving different imidazole derivatives. Herein, we developed a
2
1
three-component reaction of amidines, ynals and sodium sulfinates to produce a
series of different sulfonylated imidazoles under metal-free conditions. To the best of
our knowledge, the selective construction of different imidazoles from the same
starting materials by an additive selection has not been reported before.
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a) Our previous work: (Ag-catalyzed)
CHO
Ar2
1 N
N
N
H
R
Ar2
Ar2
N
AgOAc
Nu
Ar1
N
+
Ar
Ar1
Nu
NH
R
R
Nu = OR, NHR, OCOR.
Ar
O
b) This work: (transition-metal-free)
R1
S
N
AcOH
O
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
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Ar2
H
CHO
Ar
N
N
Ar2
O
Ar1
Ar1
+
S
Control
TBHP
+
R1
NH
ONa
N
Ar
Ar2
N
Ar1
O
S
O
R1
Scheme 1. Synthesis of imidazole derivatives from amidines, ynals and nucleophilic
reagents.
With the optimized reaction conditions in hand (Table S1 in Surporting
Information, entry 8), we first probed the scope for the formation of sulfonylated
2
2
imidazoles by using different amidines which has been reported. The results were
showed in Scheme 2. Various N-substituted benzimidamides were employed and the
desired products 4aa-4az were obtained in 56-83% yields. Electron-rich groups on the
1
benzene ring of N-substituted amidines (Ar ) such as Me or OMe all worked well and
led to the corresponding imidazoles 4aa-4ae and 4ak in 66-83% yields. Electron-poor
1
groups on the benzene ring of N-substituted amidines (Ar ) such as F, Cl or Br were
also tolerated and the yields of products ranged from 72% to 75% (4af-4aj and 4al).
Furthermore, various substrates with electron-withdrawing and electron-donating
2
groups on the other benzene ring of N-substituted amidines (Ar ) all worked well
(4am-4ap). In particular, multi-substituted amidines also underwent these cascade
annulations smoothly to generate the target products in 56-80% yields (4aq-4az).
Unfortunately, when alkyl amidines were used as substrates, the desired products
were not detected.
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Ph
O
S
H
CHO
2
O
S
N
Ar
AcOH
ONa EtOH, 70
℃ , 4 h
Ph
Ph
Ar1
+
N
O
+
Ph
NH
Ar2
Ph
2a
N
4 Ar
1
3a
1
Ph
O
S
Ph
O
S
Ph
O
S
Ph
Ph
N
N
N
O
O
O
Ph
Ph
O
Ph
R
N
N
N
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R
4
aa, R = H, 83%
4af, R = Cl, 75%
4
ab, R = o-Me, 80%
ac, R = m-Me, 79%
4ad, R = p-Me, 78%
4
ae, 66%
4
4ag, R = Br, 72%
Ph
O
O
Ph
Ph
O
S
S
Ph
S
Ph
N
Ph
O
N
O
N
Ph
O
N
N
Ph
N
R
Ph
4
am, R = o-Me, 80%
4an, R = p-Me, 78%
ao, R = p-OMe, 73%
4ap, R = p-F, 75%
Cl
4
Cl
4ai
R
4al, 74%
Ph
O
4ah, R = F, 74%
ai, R = Cl, 75%
aj, R = Br, 72%
Ph
O
S
S
Ph
4
4
Ph
N
O
N
N
O
4ak, R = OMe, 79%
N
Ph
O
S
R1
PhR1
N
N
O
R
4ar, R = Me, R1= m-Me, 80%
4as, R = Cl, R1= m-Me, 76%
at, R = Cl, R1= p-OMe, 74%
R
Cl
4
4
4ax, R =F, R1= m-Me, 79%
ay, R =F, R1= p-Me, 80%
au, R = Br, R1= m-Me, 77%
4
4av, R = Br, R1= p-OMe, 71%
4aw, R = Br, R = p-Cl, 75% 4az, R =Br, R1= n-Me, 56%
4
aq, 72%
1
Scheme 2. Substrate scope of amidines
Subsequently, we examined different sodium sulfinates in this reaction for the
synthesis of imidazoles, and the results are summarized in Scheme 3. A series of
sodium sulfinates reactions proceeded smoothly under the standard conditions
reaction, giving the desired products 4ba-4na in good yields. We were pleased to find
that sodium sulfinates with either electron-rich or electron-withdrawing groups on the
benzene ring all afforded the corresponding products in good yields (50-81%,
4
ba-4ia). Then cyclopropyl and thienyl sodium sulfinates were tested and expected
products 4ja and 4ka were formed in 67% and 73% yields, respectively. Moreover,
multi-substituted imidazole products 4la-4na were also obtained in moderate yields of
6
0-78%.
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Ar
O
S
CHO
R1
H
O
N
Ph
AcOH
N
Ph
S
O
+
+
R1 ONa
EtOH, 70 ℃ , 4 h
NH
Ph
N
Ar
2
Ph
1
a
3
4
Ph
O
Ph
O
S
Ph
O
S
S
R
N
N
N
O
O
O
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
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8
9
0
1
2
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9
0
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2
3
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0
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2
3
4
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0
R
R
Ph
Ph
Ph
N
N
N
Ph
ba, R = o-Me, 79%
4ca, R = p-Me, 66%
Ph
Ph
4
4da, R = F, 80%
4ea, R = CF3, 78%
4fa, R = OMe, 50%
4
4
ga R = Br, 81%
ha, R = CF , 80%
3
Ph
O
S
O
O
Ph
O
S
Ph
S
S
Cl
F
N
F
N
N
O
O
Ph
N
Ph
Ph
F
N
N
Ph
Ph
Ph
4ia, 72%
4ja, 67%
4ka, 73%
Ph
O
S
O
O
S
O
O
S
O
N
N
N
Ph
Ph
Ph
N
N
N
Cl
4ma, 78%
Cl
4
la, 68%
4na, 60%
Scheme 3. Substrate scope of sodium sulfinates
To our delight, another kind of sulfonylated imidazole was successfully achieved
o
in well yields in the presence of TBHP in MeCN at 70 C for 4 h (Scheme 4). Various
N-substituted benzimidamides were next probed. It was found that amidines with
different substitutes reacted smoothly and afforded the corresponding sulfonylated
imidazoles in good yields (5aa-5al). Subsequently, we further explored the scope of
sodium sulfinates in this MCR for the synthesis of sulfonylated imidazoles. In
perticular, reactions of sodium benzene sulfinate bearing either electron-rich or
electron-poor groups obtained the expected imidazoles in good yields (70-83%,
5
am-5av). It should be note that sodium ethyl sulfinate, sodium cyclopropane
sulfinate and sodium thiophene sulfinate were also reacted well and gave the target
products yields ranged from 67% to 87% (5aw-5ay). In addition, substituted
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phenyl-propynal successfully obtained the sulfonylated imidazoles product 5az in
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0% yield.
N
H
CHO
+
Ar2
Ar
N
O
Ar2
Ar1
TBHP
0
1
2
3
4
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9
0
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0
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0
1
2
3
4
5
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9
0
+
S
N
R1 ONa
MeCN, 70
1O
S
O
℃ , 4 h
NH
Ar
R1
Ar
1
2
3
5
N
N
N
Ph
Ph
Ph
Ph
O
N
N
N
R
O
S
O
O
S
O
O
S
Ph
R
Ph
Ph
Ph
R
R1
5
ad, R = Me , 90%
5
aa, R = H, 92%
5
5
ai, R = m-Me, R1 = F, 80%
aj, R = p-Me, R1 = F, 87%
5ak, R = o-Me, R1 = Br, 71%
al, R = p-Me, R1 = Br, 72%
5ae, R = OMe, 88%
5af, R = F, 73%
ag, R = Cl, 85%
5
ab, R = Me, 82%
ac, R = Cl, 90%
5
5
N
5
Ph
5ah, R = Br, 84%
Ph
N
N
N
Ph
Ph
O
S
O
Ph
Ph
Ph
N
N
O
S
O
O
S
O
Ph
R
5am, R = m-f, 83%
an, R = m-CF3, 80%
5ao, R = p-Me, 75%
5av
5
R
R1
5ap, R = p-OMe, 70%
5aq, R = p-Cl, 81%
5ar, R = p-Br, 83%
5as, R = p-CF3, 76%
5at, R = Me, R1 = Me, 72%
au, R = CF3, R1 = Cl, 78%
5av, 79%
5
N
N
N
Ph
Ph
N
Ph
O
Ph
O S O
Ph
N
Ph
N
O
S
O
Ph
O
S
R
Ph
S
Cl
5aw, R = Et, 67%
c
5az, 80%
5ax, R = Pr, 87%
5ay, 78%
Scheme 4. Substrate scope of amidines and sodium sulfinates
To gain further insight into the mechanism of this reaction for the synthesis of
4
ca and 5ao, control experiments were conducted to determine the dehydration
pathways (Scheme 5). First, AcOH-promoted intermolecular dehydration of 2a and 3a
has occurred to give the intermediate 6aa in 98% yield (Eqn. 1). Then 6aa was react
with 1a to generate 4ca in 66% yield (Eqn. 2). However, only trace amount of
intermediate 6aa was obtained when 2a and 3a were performed in the absence of
AcOH (Eqn. 3). In addition, when the reaction was carried out with the adding of 1
equivalent amount of AcOH and 5 equivalent amount of TEMPO or BHT in EtOH at
o
7
0 C for 4 h, the desired product 4ca was formed with the yield of 66% or 54%,
respectively (Eqn. 4). Only trace amount of product 5ao was detected with the
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addition of TEMPO or BHT under optimazied condition (Eqn. 5). Therefore, the
above results suggested that 6aa was the intermediate for the generation of 4ca, and
the formation of 5ao might involve a radical process, while 4ca is not.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
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3
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4
4
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5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
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0
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CHO
O
S
HOAc
ONa
1
)
+
O
S
CHO
H
EtOH, 70 ℃ , 2h
O
Ph
3
a
Ph
2
a
6aa, 98%
Ph
O
H
S
O
HOAc
EtOH, 70 ℃ , 4 h
N
Ph
2)
N
O
CHO+ Ph
H
S
O
Ph
NH
1a
N
Ph
Ph 4ca, 66%
6
aa
CHO
O
S
3
)
ONa
EtOH/MeCN, 70 ℃ , 2 h
+
O
S
CHO
O
Ph
2a
3a
Ph
H
6
aa trace
Ph
O
S
O
HOAC
H
N
4)
Ph
NH
1a
℃
EtOH, 70 , 4 h
N
O
CHO+ Ph
H
S
O
TEMPO, 5.0 equiv Ph
or BHT, 5.0 equiv
N
Ph
6
Ph 66% (TEMPO)
4ca, 54% (BHT)
aa
N
H
N
CHO
Ph
O
S
Ph
TBHP
Ph
N
5)
Ph
ONa
+
+
MeCN, 70
℃ , 4 h
O S O
Ph
NH
TEMPO, 5.0 equiv
or BHT, 5.0 equiv
Ph
2a
1a
3a
5ao trace
Scheme 5. Control experiments.
On the basis of all of the results and several previous references,23,24 two possible
mechanisms were proposed in Scheme 6. On one hand, for the formation of 4,
AcOH-promoted 2 converted to active station 7 at first, which underwent nucleophilic
additon25 with 3 to acquire compound 6. Then, the nucleophilic attack of 1 to 6
produce the intermediate A, which underwent intramolecular cyclization to give the
intermediate B. Finally, the desired product 4 was formed via intermolecular
dehydration (Scheme 6, Path i). On the other hand, the radical mechanism is
recommended for the synthesis of 5 (Scheme 6, Path ii). Sodium sulfinate 2 was
oxidized by TBHP to give the sulfonyl radical C. At the meanwhile, intermolecular
dehydration of 1 and 2 afforded the imine intermediate D. Subsequently,
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intramolecular annulation and protonation of intermediate D generated charged
species E. Addition of sulfonyl radical C to the intermediate E followed by
aromatization led to the formation of the final sulfonylated product 5.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
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2
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5
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7
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1
2
3
4
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7
8
9
0
1
2
3
4
5
6
7
8
9
0
i) Mechanism for the formation of 4
O
R1
CHO
CHO
S
R1 ONa
O
H+
S
CHO
H
3
O
H
-Na+
Ar
NH Ar2
Ar
Ar
7
6
2
Ar1
NH
1
Ar
O
Ar
O
Ar
O
S R1
S R1
S R1
-H2O
N
N
NH
Ar2
O
O
O
Ar2
Ar2
OH
OH
N
N
N
1
1
1
Ar
4
Ar
B
Ar
A
ii) Mechanism for the formation of 5
O
S
O
Ar
1
R SO2Na
TBHP
R1
C
t-BuO
+
NaOH
+
3
CHO
2
1NH Ar2
NH
N
-H2O
Ar
+
N
Ar1
D
H2O
Ar
2
Ar
OH
1
-
Ar2
N
N
t-BuO .
N
Ar
SO2R1 t-BuO-
Ar
Ar2
Ar2
1N +
N
Ar15
N
Ar1
SO2R1
Ar
Ar
F
E
C
Scheme 6. Possible Mechanism.
In summary, we have developed a novel additive-controlled highly regioselective
strategy for the synthesis of functional imidazoles via three-component reaction of
amidines, ynals and sodium sulfinates. On one hand, the vinyl sulfone intermediate 6
was generated under AcOH-promoted condition for affording the 4-sulfonylated
imidazole product. On the other hand, in the presence of TBHP and sodium sulfinate,
the sulfonyl radical was formed and further produced the 5-sulfonylated imidazole
with the imine intermediate D. The features of this transformation are
transition-metal-free, environmentally friendly and high atom economy, which makes
it a new valuable route to synthesize good functional group tolerance imidazole
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derivatives. Further applications of this reaction are currently underway in our
laboratory, and the result will be reported in due course.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
EXPERIMENTAL SECTION
General Methods
o
All reactions were performed in a heating mantle at 70 C in sealed tube otherwise
noted. Analytical thin layer chromatography was carried out using silica gel GF254,
1
visualized under UV light (at 254 nm). Proton NMR ( H) were recorded at 400 MHz,
13
and Carbon NMR ( C) at 100 MHz NMR spectrometer. Multiplicities are
abbreviated as: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet. TOF type of
mass analyzer was used for HRMS measurements.
General procedure
Synthesis of 1a according to the following procedure22:
Nitrile (10 mmol) is mixed with amine (10 mmol) in a 100 mL wide-mouthed flask,
AlCl (1.35 g, 10 mmol) was then added slowly during stirring. The mixture was
3
o
allowed to heat at 200 C for 30 minutes. Concentrated hydrochloric acid (0.3 mL)
and ice-water (25 mL) was then added to the hot mixture while maintaining vigorous
stirring. After the reaction was completed, the mixture was cooled externally in the
water and filtered. The filtrate was washed a stirred solution of 3.3 g of sodium
hydroxide in 18 mL of water. The flocculation precipitate was collected under
reduced pressure, washed with water, and dried to constant weight. The residue was
then purified by recrystallization.
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6
Synthesis of 4aa according to the following procedure:
A 25 mL-schlenk tube was charged with a stirring bar, and N-phenylbenzimidamide
(1a, 39.2 mg, 0.20 mmol), phenyl-propynal (2a, 26.0 mg, 0.20 mmol), sodium
benzenesulfinate(3a, 32.8 mg, 0.20 mmol ), AcOH (24.0 mg, 0.20 mmol), EtOH (2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
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9
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3
4
5
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9
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1
2
3
4
5
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7
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9
0
o
mL or 3 mL) were added. The reaction was allowed to stir at 70 C for 4 h. The crude
product was separated by column chromatography (eluted with petroleum ether : ethyl
acetate = 3:1) to give a pure sample of 4aa in a 83% yield (74.7 mg ).
Large-scale synthesis of 4ba according to the following procedure:
A 25 mL-Schlenk tube was charged with a stirring bar, and N-phenylbenzimidamide
(1a, 196.0 mg, 1.0 mmol), phenyl-propynal (2a, 130.0 mg, 1.0 mmol), sodium
p-methoxybenzenesulfinate (3a, 194.0 mg, 1.0 mmol), AcOH (120.0 mg, 1.0 mmol),
o
EtOH (3 mL) were added. The reaction was allowed to stir at 70 C for 4 h. The crude
product was separated by column chromatography (eluted with petroleum ether : ethyl
acetate = 3:1) to give a pure sample of 4ba in a 79% yield (366.5 mg).
Synthesis of 5aa according to the following procedure:
A 25 mL-schlenk tube was charged with a stirring bar, and N-phenylbenzimidamide
(1a, 39.2 mg, 0.20 mmol), phenyl-propynal (2a, 26.0 mg, 0.20 mmol), sodium
benzenesulfinate(3a, 32.8 mg, 0.20mmol ), TBHP (60.0 mg, 0.20 mmol), MeCN (2
o
mL or 3 mL) were added. The reaction was allowed to stir at 70 C for 4 h. The crude
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product was separated by column chromatography (eluted with petroleum ether : ethyl
acetate = 3:1) to give a pure sample of 5aa in a 92% yield (82.8 mg).
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
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1
2
3
4
5
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4
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1,2-diphenyl-4-(phenyl(phenylsulfonyl)methyl)-1H-imidazole 4aa (83%).
−
1
−1 1
Yellow oil, 74.7 mg. IR (cm ): 3080, 3032, 1590, 1560, 1130, 1085, 698 cm . H
NMR (400 MHz, CDCl ) δ 7.68-7.66 (m, 2H), 7.61 (s, 1H), 7.56-7.51 (m, 3H),
3
1
3
7
.41-7.37 (m, 5H), 7.30-7.28 (m, 3H), 7.25-7.17 (m, 7H), 5.63 (s, 1H). C {1H}
NMR (100MHz, CDCl ) δ 147.8, 137.6, 135.7, 133.8, 130.7, 130.5, 130.3, 130.3,
3
129.9, 129.8, 129.7, 129.7, 129.5, 129.5, 129.2, 128.8, 128.8, 128.8, 128.8, 128.6,
1
28.6, 128.2, 128.2, 128.2, 128.2, 128.1, 126.1, 67.3. HRMS ESI (m/z): calcd for
+
C H N O S [M + H] : 452.1506, found: 452.1510.
2
8
23
2
2
2-phenyl-4-(phenyl(phenylsulfonyl)methyl)-1-(o-tolyl)-1H-imidazole 4ab (80%).
−1
−1 1
Yellow oil, 74.3 mg. IR (cm ): 3071, 3032, 1503, 1444, 1314, 1152, 770 cm . H
NMR (400 MHz, CDCl ) δ 7.79-7.67 (m, 2H), 7.63-7.53 (m, 3H), 7.46-7.27 (m,
3
1
3
1
0H), 7.24-7.14 (m, 5H), 5.67 (s, 1H), 1.90 (s, 3H). C {1H} NMR (100 MHz,
CDCl ) δ 146.6, 137.4, 134.9, 133.4, 133.4, 131.4, 130.6, 130.6, 129.9, 129.4, 129.4,
3
1
1
+
29.4, 128.8, 128.8, 128.6, 128.5, 128.4, 128.2, 128.2, 128.2, 127.8, 127.7, 127.6,
27.5, 127.5, 127.2, 122.9, 71.8, 17.6. HRMS ESI (m/z): calcd for C H N O S [M
2
9
25
2
2
+
H] : 465.1631, found: 465.1632.
2
-phenyl-4-(phenyl(phenylsulfonyl)methyl)-1-(m-tolyl)-1H-imidazole 4ac (79%).
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2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
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4
4
4
4
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5
5
5
5
5
5
5
5
5
5
6
−
1
−1 1
Yellow oil, 73.3 mg. IR (cm ): 3063, 3016, 1513, 1506, 1306, 1052, 687 cm . H
NMR (400 MHz, CDCl ) δ 7.68-7.66 (m, 2H), 7.59 (s, 1H), 7.54-7.51 (m, 3H),
3
7
.40-7.36 (m, 2H), 7.32-7.27 (m, 4H), 7.25-7.14 (m, 6H), 7.07 (s, 1H), 6.95 (d, J =
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
7.6 Hz, 1H), 5.63 (s, 1H), 2.34 (s, 3H). C {1H} NMR (100 MHz, CDCl ) δ 146.2,
3
1
39.8, 138.1, 138.0, 133.7, 133.5, 132.3, 130.5, 130.5, 129.8, 129.4, 129.4, 129.3,
129.2, 128.7, 128.7, 128.7 128.6, 128.6, 128.6, 128.5, 128.5, 128.1, 128.1, 126.3,
+
1
4
23.1, 122.9, 71.8, 21.3. HRMS ESI (m/z): calcd for C H N O S [M + H] :
2
9
25
2
2
65.1631, found: 465.1637.
2
-phenyl-4-(phenyl(phenylsulfonyl)methyl)-1-(p-tolyl)-1H-imidazole 4ad (78%).
o
−1
White solid, bp. 96.4-97.2 C. 72.4 mg. IR (cm ): 3063, 3032, 1513, 1506, 1318,
−
1 1
1152, 787 cm . H NMR (400 MHz, CDCl ) δ 7.69-7.67 (m, 2H), 7.59 (s, 1H),
3
7
.57-7.52 (m, 3H), 7.41-7.37 (m, 2H), 7.34-7.26 (m, 5H), 7.25-7.18 (m, 5H), 7.09 (d,
13
J = 8.4 Hz, 2H), 5.64 (s, 1H), 2.39 (s, 3H). C {1H} NMR (100 MHz, CDCl ) δ
3
1
1
46.2, 138.5, 138.1, 135.6, 133.6, 133.5, 132.3, 130.5, 130.5, 130.1, 130.1, 129.8,
29.4, 129.4,128.7, 128.7, 128.7, 128.6, 128.5, 128.5, 128.5, 128.5, 128.2, 128.2,
+
125.7, 125.7, 123.0, 71.8, 21.2. HRMS ESI (m/z): calcd for C H N O S [M + H] :
2
9
25
2
2
4
65.1631, found: 465.1631.
1
4
-(2-methoxyphenyl)-2-phenyl-4-(phenyl(phenylsulfonyl)methyl)-1H-imidazole
ae (66%).
−
1
Yellow oil, 63.4 mg. IR (cm ): 3035, 3016, 1527, 1507, 1341, 1286, 1144, 1081, 694
−1
1
cm . H NMR (400 MHz, CDCl ) δ 7.74-7.69 (m, 2H), 7.60-7.53 (m, 4H), 7.43-7.38
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(m, 3H), 7.34-7.30 (m, 3H), 7.24-7.14 (m, 6H), 7.01-6.95 (m, 2H), 5.67 (s, 1H), 3.59
1
3
(
s, 3H). C {1H} NMR (100 MHz, CDCl ) δ 149.2, 142.2, 133.4, 128.6, 128.6,
3
1
27.2, 125.9, 125.9, 125.6, 124.7, 124.7, 124.0, 124.0, 123.7, 123.7, 123.7, 123.7,
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
123.4, 123.4, 123.3, 123.3, 123.1, 123.1, 122.2, 118.6, 116.2, 107.7, 66.9, 50.8.
+
HRMS ESI (m/z): calcd for C H N O S [M + H] : 481.1580, found: 481.1584.
2
9
25
2
3
1
-(3-chlorophenyl)-2-phenyl-4-(phenyl(phenylsulfonyl)methyl)-1H-imidazole 4af
(75%).
o
−1
White solid, bp. 163.8-165.1 C. 72.6 mg. IR (cm ): 3055, 3030, 1543, 1515, 1373,
−1
1
1
7
1
152, 782, 703 cm . H NMR (400 MHz, CDCl ) δ 7.68-7.65 (m, 2H), 7.61 (s, 1H),
3
.57-7.49 (m, 3H), 7.42- 7.26 (m, 11H), 7.25-7.21 (m, 2H), 7.08-7.05 (m, 1H), 5.61 (s,
13
H). C {1H} NMR (100 MHz, CDCl ) δ 146.3, 139.1, 137.9, 135.2, 134.2, 133.5,
3
132.2, 130.6, 130.5, 130.5, 129.3, 129.3, 129.3, 129.0, 128.8, 128.7, 128.7, 128.7,
1
28.6, 128.6, 128.5, 128.5, 128.4, 128.4, 126.0, 124.3, 122.5, 71.7. HRMS ESI
+
(
m/z): calcd for C H ClN O S [M + H] : 485.1085, found: 485.1090.
2
8
22
2
2
1-(3-bromophenyl)-2-phenyl-4-(phenyl(phenylsulfonyl)methyl)-1H-imidazole 4ag
(72%).
o
−1
White solid, bp. 190.3-190.8 C. 76.0 mg. IR (cm ): 3057, 3031, 1543, 1514, 1303,
−
1 1
1152, 789, 585 cm . H NMR (400 MHz, CDCl ) δ 7.69-7.65 (m, 2H), 7.60 (s, 1H),
3
7
.57-7.37 (m, 8H), 7.36-7.27 (m, 5H), 7.26-7.21 (m, 3H), 7.11-7.09 (m, 1H), 5.61 (s,
1
3
1H). C {1H} NMR (100 MHz, CDCl ) δ 146.3, 139.2, 137.9, 134.2, 133.5, 133.5,
3
1
32.2, 131.6, 130.8, 130.5, 130.5, 129.5, 129.5, 129.3, 128.9, 128.8, 128.8, 128.8,
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1
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1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
128.6, 128.6, 128.5, 128.5, 128.3, 128.3, 124.8, 122.9, 122.5, 71.7. HRMS ESI
+
(
m/z): calcd for C H BrN O S [M + H] : 529.0580, found: 529.0576.
2
8
22
2
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
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4
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6
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0
1
2
3
4
5
6
7
8
9
0
1
-(4-fluorophenyl)-2-phenyl-4-(phenyl(phenylsulfonyl)methyl)-1H-imidazole 4ah
(74%).
o
−1
Yellow solid, bp. 178.6-179.7 C. 69.3 mg. IR (cm ): 3059, 3032, 1543, 1515, 1373,
−1
1
1
252, 1152, 782 cm . H NMR (400 MHz, CDCl ) δ 7.70-7.65 (m, 2H), 7.61-7.60
3
(m, 1H), 7.57-7.50 (m, 3H), 7.42-7.27 (m, 8H), 7.23-7.19(m, 4H), 7.13-7.08 (m, 2H),
1
3
5
1
1
.64 (s, 1H). C {1H} NMR (100 MHz, CDCl ) δ 162.17 (d, J = 248.8 Hz), 146.4,
3
37.9, 134.12 (d, J = 3.2 Hz), 133.8, 133.5, 133.5, 132.2, 130.5, 130.5, 129.3, 129.3,
28.8, 128.8, 128.7, 128.7, 128.6, 128.6, 128.5, 128.5, 128.3, 128.3, 127.8, 127.72 (d,
J = 8.7 Hz), 122.8, 116.7, 116.5, 71.7. HRMS ESI (m/z): calcd for C H FN O S [M
2
8
22
2
2
+
+ H] : 469.1381, found: 469.1384.
1
-(4-chlorophenyl)-2-phenyl-4-(phenyl(phenylsulfonyl)methyl)-1H-imidazole 4ai
(75%).
o
−1
Yellow solid, bp. 109-110 C. 72.6 mg. IR (cm ): 3056, 3033, 1541, 1517, 1370,
−
1 1
1
7
157, 768, 702 cm . H NMR (400 MHz, CDCl ) δ 7.68-7.64 (m, 2H), 7.60 (s, 1H),
3
.56-7.50 (m, 3H), 7.41-7.35 (m, 4H), 7.30-7.27 (m, 4H), 7.26-7.20 (m, 4H),
1
3
7.16-7.14 (m, 2H), 5.61 (s, 1H). C {1H} NMR (100 MHz, CDCl ) δ 146.3, 137.8,
3
1
36.5, 134.4, 133.5, 133.5, 132.2, 130.4, 130.4, 129.8, 129.8, 129.3, 129.3, 129.0,
129.0, 128.8, 128.8, 128.6, 128.6, 128.5, 128.5, 128.4, 128.4, 127.1, 127.1, 122.5,
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+
122.5, 71.6. HRMS ESI (m/z): calcd for C H ClN O S [M + H] : 485.1085, found:
2
8
22
2
2
4
85.1089.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
-(4-bromophenyl)-2-phenyl-4-(phenyl(phenylsulfonyl)methyl)-1H-imidazole 4aj
(72%).
o
−1
White solid, bp. 189.4-190.2 C. 76.0 mg. IR (cm ): 3056, 3031, 1543, 1514, 1303,
−1
1
1
152, 789, 588 cm . H NMR (400 MHz, CDCl ) δ 7.67-7.66 (m, 2H), 7.60 (s, 1H),
3
7.57-7.48 (m, 5H), 7.41- 7.38 (m, 2H), 7.31-7.27 (m, 5H), 7.25-7.24 (m, 3H),
1
3
7
.12-7.10 (m, 2H), 5.60 (s, 1H). C {1H} NMR (100 MHz, CDCl ) δ 146.3, 137.9,
3
1
37.1, 134.1, 133.5, 132.8, 132.8, 132.2, 130.4, 130.4, 129.4, 129.3, 129.3, 128.9,
28.8, 128.8, 128.8, 128.6, 128.6, 128.5, 128.5, 128.4, 128.4, 127.4, 127.4, 122.4,
1
+
1
22.3, 71.7. HRMS ESI (m/z): calcd for C H BrN O S [M + H] : 529.0580, found:
2
8
22
2
2
529.0576.
1
4
-(4-methoxyphenyl)-2-phenyl-4-(phenyl(phenylsulfonyl)methyl)-1H-imidazole
ak (79%).
o
−1
White solid, bp. 96.1-96.8 C. 75.9 mg. IR (cm ): 3033, 3016, 1547, 1517, 1348,
−
1
1
1
216, 1144, 1085, 683 cm . H NMR (400 MHz, CDCl ) δ 7.70-7.65 (m, 2H),
3
7
.55-7.51 (m, 4H), 7.40-7.36 (m, 2H), 7.30-7.26 (m, 4H), 7.25-7.24 (s, 1H), 7.23-7.17
1
3
(m, 3H), 7.14-7.11 (m, 2H), 6.90-6.88 (m, 2H), 5.62 (s, 1H), 3.81 (s, 3H). C {1H}
NMR (100 MHz, CDCl ) δ 159.4, 146.3, 138.0, 133.5, 133.5, 132.3, 131.1, 130.5,
3
130.5, 129.81, 129.3, 129.3, 128.8, 128.6, 128.6, 128.6, 128.6, 128.5, 128.5, 128.5,
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
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5
5
5
5
5
5
5
6
128.2, 128.2, 127.1, 127.1, 123.2, 114.6, 114.6, 71.9, 55.6. HRMS ESI (m/z): calcd
+
for C H N O S [M + H] : 481.1580, found: 481.1584.
2
9
25
2
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
4
-(3,4-dichlorophenyl)-2-phenyl-4-(phenyl(phenylsulfonyl)methyl)-1H-imidazole
al (74%).
o
−1
White solid, bp. 127.6-128.0 C. 76.7 mg. IR (cm ): 3039, 3024, 1550, 1507, 1341,
−1
1
1
176, 793 cm . H NMR (400 MHz, CDCl ) δ 7.67-7.64(m, 2H), 7.62 (s, 1H),
3
7.57-7.53 (m, 1H), 7.50-7.45 (m, 3H), 7.4-7.37 (m, 3H), 7.34-7.27 (m, 8H), 7.05-7.02
1
3
(
m, 1H), 5.66 (s, 1H). C {1H} NMR (100MHz, CDCl ) δ 146.3, 137.7, 137.1,
3
1
34.1, 133.7, 133.6, 133.0, 132.1, 131.2, 131.2, 130.4, 130.4, 129.3, 129.3, 128.9,
28.8, 128.8, 128.6, 128.6, 128.5, 128.5, 128.5, 127.5, 127.5, 125.3, 125.3, 122.3,
1
+
7
1.3. HRMS ESI (m/z): calcd for C H Cl N O S [M + H] : 519.0695, found:
2
8
21
2
2
2
519.0695.
1
-phenyl-4-(phenyl(phenylsulfonyl)methyl)-2-(o-tolyl)-1H-imidazole 4am (80%).
o
−1
White solid, bp. 145.3-146.0 C. 74.3 mg. IR (cm ): 3071, 3032, 1503, 1434, 1314,
−
1 1
1
152, 780 cm . H NMR (400 MHz, CDCl ) δ 7.74-7.70 (m, 2H), 7.68 (s, 1H),
3
7
.63-7.58 (m, 2H), 7.54-7.51(m, 1H), 7.42-7.27 (m, 7H), 7.26-7.25 (m, 1H), 7.21-7.17
1
3
(m, 1H), 7.09-7.02 (m, 5H), 5.65 (s, 1H), 1.90 (s, 3H). C {1H} NMR (100 MHz,
CDCl ) δ 146.2, 138.2, 137.8, 137.6, 133.6, 133.5, 132.0, 130.8, 130.8, 130.6, 130.6,
3
1
1
+
30.3, 129.8, 129.3, 129.3, 129.3, 129.3, 128.8, 128.7, 128.7, 128.6, 128.6, 127.9,
25.5, 124.6, 124.6, 121.0, 71.8, 19.9. HRMS ESI (m/z): calcd for C H N O S [M
29 25
2
2
+
H] : 465.1631, found: 465.1634.
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-phenyl-4-(phenyl(phenylsulfonyl)methyl)-2-(p-tolyl)-1H-imidazole 4an (78%).
−
1
−1 1
Yellow oil. 72.4 mg. IR (cm ): 3063, 3037, 1535, 1516, 1314, 1148, 767 cm . H
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
NMR (400 MHz, CDCl ) δ 7.70-7.66 (m, 2H), 7.60 (s, 1H), 7.56-7.52 (m, 3H),
3
7
7
.41-7.37 (m, 5H), 7.31-7.27 (m, 3H), 7.23-7.20 (m, 2H), 7.15-7.14 (m, 2H),
1
3
.02-7.00 (m, 2H), 5.63 (s, 1H), 2.28 (s, 3H). C {1H} NMR (100 MHz, CDCl ) δ
3
146.4, 138.6, 138.2, 138.0, 133.6, 133.5, 132.3, 130.5, 130.5, 129.5, 129.5, 129.3,
1
1
4
29.3, 128.9, 128.9, 128.7, 128.6, 128.6, 128.5, 128.5, 128.5, 128.5, 128.4, 126.8,
+
25.9, 125.9, 122.6, 71.8, 21.3. HRMS ESI (m/z): calcd for C H N O S [M + H] :
2
9
25
2
2
65.1631, found: 465.1634.
2
4
-(4-methoxyphenyl)-1-phenyl-4-(phenyl(phenylsulfonyl)methyl)-1H-imidazole
ao (73%).
−
1
Yellow oil. 70.1 mg. IR (cm ): 3033, 3016, 1527, 1507, 1348, 1226, 1144, 1083, 693
−
1 1
cm . H NMR (400 MHz, CDCl ) δ 7.68-7.66 (m, 2H), 7.58-7.51 (m, 4H), 7.40-7.36
3
(m, 5H), 7.30-7.28 (m, 3H), 7.22-7.17 (m, 4H), 6.74-6.71 (m, 2H), 5.61 (s, 1H), 3.74
1
3
(s, 3H). C {1H} NMR (100 MHz, CDCl ) δ 159.9, 146.2, 138.2, 138.1, 133.4,
3
1
33.4, 132.3, 130.5, 130.5, 130.1, 130.1, 129.5, 129.5, 129.3, 129.3, 128.7, 128.7,
128.5, 128.5, 128.5, 128.5, 128.4, 125.9, 125.9, 122.4, 122.2, 113.6, 71.8, 55.2.
+
HRMS ESI (m/z): calcd for C H N O S [M + H] : 481.1580, found: 481.1583.
2
9
25
2
3
2
-(4-fluorophenyl)-1-phenyl-4-(phenyl(phenylsulfonyl)methyl)-1H-imidazole 4ap
(75%).
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2
2
2
2
2
2
2
2
3
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3
3
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5
5
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5
5
6
o
−1
Yellow solid, bp. 154.8-155.0 C.70.2 mg. IR (cm ): 3045, 3036, 1542, 1505, 1373,
−
1 1
1
7
232, 1142, 786 cm . H NMR (400 MHz, CDCl ) δ 7.69-7.64 (m, 2H), 7.61 (s, 1H),
3
.57-7.50 (m, 3H), 7.43 -7.37 (m, 5H), 7.31- 7.27 (m, 3H), 7.24-7.16 (m, 6H), 5.60 (s,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
1H). C {1H} NMR (100 MHz, CDCl ) δ 146.37 (d, J = 235.0 Hz), 137.89 (d, J =
3
5
.5 Hz), 134.7, 134.0, 133.5, 132.21 (d, J = 2.3 Hz), 130.5, 130.5, 129.9, 129.9, 129.8,
129.8, 129.4, 129.4, 128.8, 128.8, 128.6, 128.6, 128.6, 128.5, 128.5, 128.5, 128.2,
28.2, 125.9, 125.9, 123.2, 71.8. HRMS ESI (m/z): calcd for C H FN O S [M +
1
2
8
22
2
2
+
H] : 469.1381, found: 469.1385.
2
-(4-chlorophenyl)-4-(phenyl(phenylsulfonyl)methyl)-1-(o-tolyl)-1H-imidazole
4aq (72%).
Yellow solid, bp. 82.6-83.1 C. 71.7 mg. IR (cm ): 3063, 3039, 1547, 1511, 1306,
o
−1
−1
1
1
152, 797 cm . H NMR (400 MHz, CDCl ) δ 7.74-7.67 (m, 2H), 7.58-7.56 (m, 3H),
3
1
3
7.47-7.28 (m, 10H), 7.24- 7.13 (m, 4H), 5.67 (s, 1H), 1.90 (s, 3H). C {1H} NMR
(
100 MHz, CDCl ) δ 137.0, 137.0, 134.8, 134.8, 134.0, 133.8, 133.6, 133.5, 133.4,
3
131.5, 131.5, 130.6, 130.6, 129.7, 129.4, 128.9, 128.9, 128.6, 128.6, 128.6, 128.4,
1
28.2, 128.1, 127.5, 127.4, 127.4, 123.1, 71.5, 17.5. HRMS ESI (m/z): calcd for
+
C H ClN O S [M + H] : 499.1242, found: 499.1246.
2
9
24
2
2
4
-(phenyl(phenylsulfonyl)methyl)-1,2-di-m-tolyl-1H-imidazole 4ar (80%).
Yellow oil. 72.7 mg. IR (cm ): 3063, 3035, 1542, 1506, 1316, 1052, 685 cm . 1H
−
1
−1
NMR (400 MHz, CDCl ) δ 7.71-7.68 (m, 2H), 7.60 (s, 1H), 7.56-7.52 (m, 3H),
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7.42-7.38 (m, 2H), 7.31-7.27 (m, 3H), 7.26-7.22 (m, 2H), 7.21-7.19 (m, 1H),
7
2
.08-7.02 (m, 3H), 6.97- 6.96(m, 1H), 6.93- 6.89 (m, 1H), 5.65 (s, 1H), 2.36 (s, 3H),
13
.25 (s, 3H). C {1H} NMR (100MHz, CDCl ) δ 146.3, 139.7, 138.1, 138.1, 138.0,
3
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
133.5, 133.5, 132.3, 130.5, 130.5, 129.6, 129.5, 129.4, 129.3, 129.3, 129.2, 129.2,
1
28.7, 128.6, 128.6, 128.5, 128.5, 127.8, 126.3, 125.6, 123.1, 122.7, 71.8, 21.3, 21.3.
+
HRMS ESI (m/z): calcd for C H N O S [M + H] : 479.1788, found: 479.1791.
3
0
27
2
2
1
4
-(3-chlorophenyl)-4-(phenyl(phenylsulfonyl)methyl)-2-(m-tolyl)-1H-imidazole
as (76%).
−
1
−1
Yellow oil. 75.7 mg. IR (cm ): 3063, 3035, 1542, 1507, 1318, 1152, 1085, 793 cm .
1
H NMR (400 MHz, CDCl ) δ 7.68-7.66 (m, 2H), 7.60 (s, 1H), 7.56-7.54 (m, 1H),
3
7
3
.53-7.50 (m, 2H), 7.41 -7.36(m, 4H), 7.32-7.28 (m, 4H), 7.23 (s, 1H), 7.10-7.04 (m,
13
H), 6.91-6.89 (m, 1H), 5.62 (s, 1H), 2.26 (s, 3H). C {1H} NMR (100 MHz, CDCl )
3
δ 146.5, 139.1, 138.2, 138.0, 135.1, 134.1, 133.5, 132.2, 130.5, 130.4, 130.4, 129.7,
1
1
29.5, 129.3, 129.3, 129.2, 128.8, 128.6, 128.6, 128.6, 128.5, 128.5, 128.0, 125.9,
25.7, 124.3, 122.4, 71.8, 21.4. HRMS ESI (m/z): calcd for C H ClN O S [M +
2
9
24
2
2
+
H] : 499.1242, found: 499.1244.
1
-(3-chlorophenyl)-2-(4-methoxyphenyl)-4-(phenyl(phenylsulfonyl)methyl)-1H-i
midazole 4at (74%).
−
1
−1
Yellow oil. 76.1 mg. IR (cm ): 3067, 3039, 1550, 1511, 1342, 1148, 845, 687 cm .
1
H NMR (400 MHz, CDCl ) δ 7.67-7.65 (m, 2H), 7.57 (s, 1H), 7.54-7.49 (m, 3H),
3
7.41-7.36 (m, 4H), 7.33-7.31 (m, 1H), 7.30-7.28 (m, 3H), 7.20-7.18 (m, 2H),
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2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
3
7.08-7.06 (m, 1H), 6.77-7.74(m, 2H), 5.59 (s, 1H), 3.76 (s, 3H). C {1H} NMR (100
MHz, CDCl ) δ 160.1, 146.3, 139.2, 137.9, 135.1, 133.9, 133.5, 132.2, 130.5, 130.5,
3
1
30.5, 130.1, 130.1, 129.3, 129.3, 128.8, 128.6, 128.6, 128.6, 128.5, 128.5, 128.4,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
126.0, 124.3, 122.1, 121.8, 113.8, 71.7, 55.3. HRMS ESI (m/z): calcd for
+
C H ClN O S [M + H] : 515.1191, found: 515.1189.
2
9
24
2
3
1
4
-(3-bromophenyl)-4-(phenyl(phenylsulfonyl)methyl)-2-(m-tolyl)-1H-imidazole
au (77%).
−
1
−1 1
Yellow oil. 83.5 mg. IR (cm ): 3063, 3034, 1542, 1506, 1315, 1142, 587 cm . H
NMR (400 MHz, CDCl ) δ 7.69-7.65 (m, 2H), 7.60 (s, 1H), 7.57-7.49 (m, 4H),
3
7
7
.46-7.45 (m, 1H), 7.42-7.38 (m, 2H), 7.31-7.29 (m, 3H), 7.25-7.21 (m, 2H),
1
3
.12-7.06 (m, 3H), 6.93-6.89 (m, 1H), 5.63 (s, 1H), 2.27 (s, 3H). C {1H} NMR (100
MHz, CDCl ) δ 146.4, 139.2, 138.2, 137.9, 134.0, 133.5, 132.2, 131.6, 130.7, 130.4,
3
130.4, 129.8, 129.5, 129.1, 129.3, 129.0, 128.8, 128.7, 128.6, 128.6, 128.5, 128.5,
1
28.1, 125.7, 124.8, 122.8, 122.4, 71.6, 21.4. HRMS ESI (m/z): calcd for
+
C H BrN O S [M + H] : 543.0736, found: 543.0746.
2
9
24
2
2
1
-(3-bromophenyl)-2-(4-methoxyphenyl)-4-(phenyl(phenylsulfonyl)methyl)-1H-i
midazole 4av (71%).
−
1
−1
Yellow oil. 72.2 mg. IR (cm ): 3063, 3036, 1548, 1508, 1312, 1138, 1082, 587 cm .
1
H NMR (400 MHz, CDCl ) δ 7.68-7.64 (m, 2H), 7.57 (s, 1H), 7.55-7.48 (m, 4H),
3
7
7
.46-7.45 (m, 1H), 7.41-7.37 (m, 2H), 7.31-7.27 (m, 3H), 7.25-7.18 (m, 3H),
13
.12-7.09 (m, 1H), 6.78-7.75(m, 2H), 5.60 (s, 1H), 3.77 (s, 3H). C {1H} NMR (100
MHz, CDCl ) δ 160.1, 146.3, 139.3, 137.9, 133.8, 133.5, 132.2, 131.5, 130.7, 130.4,
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130.4, 130.2, 130.2, 129.3, 129.3, 128.8, 128.8, 128.6, 128.6, 128.5, 128.5, 124.8,
1
22.9, 122.1, 121.7, 113.8, 113.8, 71.7, 55.3. HRMS ESI (m/z): calcd for
+
C H BrN O S [M + H] : 559.0686, found: 559.0688.
2
9
24
2
3
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
-(3-bromophenyl)-2-(4-chlorophenyl)-4-(phenyl(phenylsulfonyl)methyl)-1H-imi
dazole 4aw (75%).
o
−1
White solid, bp. 92.0-92.6 C. 84.3 mg. IR (cm ): 3031, 3015, 1530, 1511, 1349,
−1
1
1
050, 730, 568 cm . H NMR (400 MHz, CDCl ) δ 7.66-7.63 (m, 2H), 7.57-7.52 (m,
3
1H), 7.57-7.53 (m, 2H), 7.50-7.46 (m, 3H), 7.41-7.37 (m, 2H), 7.33-7.27 (m, 4H),
.25-7.22 (m, 4H), 7.12-7.09 (m, 1H), 5.58 (s, 1H). 13C {1H} NMR (100MHz,
CDCl ) δ 145.2, 139.0, 137.8, 135.1, 134.3, 133.6, 132.1, 131.9, 130.9, 130.4, 130.4,
7
3
1
1
29.9, 129.9, 129.3, 129.3, 128.9, 128.8, 128.7, 128.7, 128.6, 128.6, 128.5, 128.5,
27.8, 124.8, 123.1, 122.9, 71.6. HRMS ESI (m/z): calcd for C H ClBrN O S [M +
2
8
21
2
2
+
H] : 563.0190, found: 563.0191.
1
4
-(4-fluorophenyl)-4-(phenyl(phenylsulfonyl)methyl)-2-(o-tolyl)-1H-imidazole
ax (79%).
o
−1
Yellow solid, bp. 80.7-81.2 C. 76.2 mg. IR (cm ): 3045, 3031, 1536, 1507, 1336,
−
1 1
1
7
7
248, 1144, 703 cm . H NMR (400 MHz, CDCl ) δ 7.69-7.65 (m, 2H), 7.60 (s, 1H),
3
.56-7.50 (m, 3H), 7.41-7.37 (m, 2H), 7.31-7.28 (m, 3H), 7.22-7.18 (m, 3H),
1
3
.11-7.06 (m, 4H), 6.91-6.87 (m, 1H), 5.65 (s, 1H), 2.25 (s, 3H). C {1H} NMR (100
MHz, CDCl ) δ 162.13 (d, J = 249.1 Hz), 146.5, 138.06 (d, J = 21.1 Hz), 134.16 (d, J
3
= 3.2 Hz), 133.7, 133.5, 132.2, 130.4, 130.4, 129.6, 129.5, 129.3, 129.3, 129.2, 128.9,
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128.8, 128.8, 128.7, 128.6, 128.6, 128.5, 128.0, 127.71 (d, J = 8.7 Hz), 125.7, 122.7,
+
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16.6, 116.4, 71.7, 21.3. HRMS ESI (m/z): calcd for C H FN O S [M + H] :
2
9
24
2
2
83.1537, found: 483.1543.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
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0
1
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1
4
-(4-fluorophenyl)-4-(phenyl(phenylsulfonyl)methyl)-2-(p-tolyl)-1H-imidazole
ay (80%).
−
1
−1
Yellow oil. 77.2 mg. IR (cm ): 3041, 3028, 1524, 1503, 1324, 1238, 1128, 753 cm .
1
H NMR (400 MHz, CDCl ) δ 7.68-7.65 (m, 2H), 7.58-7.50 (m, 4H), 7.41-7.36 (m,
3
2H), 7.31-7.27 (m, 3H), 7.22-7.18 (m, 2H), 7.15-7.07 (m, 4H), 7.04-7.02 (m, 2H),
1
3
5
.63 (s, 1H), 2.29 (s, 3H). C {1H} NMR (100 MHz, CDCl ) δ 162.11 (d, J = 249.1
3
Hz), 146.6, 138.38 (d, J = 88.0 Hz), 137.9, 134.24 (d, J = 3.2 Hz), 133.7, 133.5, 133.5,
1
1
32.3, 132.3, 130.5, 130.5, 129.3, 129.0, 128.8, 128.6, 128.6, 128.6, 128.6, 128.5,
28.5, 127.8, 127.7, 126.5, 122.6, 116.6, 116.4, 71.7, 21.3. HRMS ESI (m/z): calcd
+
for C H FN O S [M + H] : 483.1537, found: 483.1542.
2
9
24
2
2
1
4
-(4-bromophenyl)-4-(phenyl(phenylsulfonyl)methyl)-2-(o-tolyl)-1H-imidazole
az (56%).
−
1
−1 1
Yellow oil. 60.7 mg. IR (cm ): 3063, 3034, 1542, 1506, 1315, 1142, 587 cm . H
NMR (400 MHz, CDCl ) δ 7.69-7.67 (m, 2H), 7.58-7.53 (m, 4H), 7.40-7.38 (m, 2H),
3
7
.30-7.28 (m, 3H), 7.24-7.12 (m, 6H), 7.10-7.08 (m, 2H), 5.65 (s, 1H), 2.38 (s, 3H).
1
3
C {1H} NMR (100 MHz, CDCl ) δ 146.2, 138.6, 138.0, 135.5, 133.5, 133.5, 132.3,
3
1
30.5, 130.5, 130.2, 130.2, 129.7, 129.4, 129.4, 128.8, 128.7, 128.7, 128.6, 128.6,
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128.6, 128.5, 128.5, 128.2, 128.2, 125.7, 125.7, 123.0, 71.7, 21.2. HRMS ESI (m/z):
+
calcd for C H BrN O S [M + H] : 543.0736, found: 543.0746.
2
9
24
2
2
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
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5
6
0
1
2
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7
8
9
0
1
2
3
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7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
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6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
,2-diphenyl-4-(phenyl(o-tolylsulfonyl)methyl)-1H-imidazole 4ba (79%).
−
1
−1 1
Yellow oil. 366.5 mg. IR (cm ): 3059, 3036, 1511, 1503, 1310, 1148, 640 cm . H
NMR (400 MHz, CDCl ) δ 7.70-7.68 (m, 1H), 7.65 (s, 1H), 7.53-7.51 (m, 2H),
3
7.44-7.38 (m, 4H), 7.30-7.28 (m, 3H), 7.25-7.15 (m, 9H), 5.72 (s, 1H), 2.64 (s, 3H).
1
3
C {1H} NMR (100 MHz, CDCl ) δ 146.2, 139.2, 138.1, 136.1, 133.7, 133.5, 132.3,
3
1
1
32.1, 131.6, 130.5, 130.5, 129.7, 129.6, 129.6, 128.8, 128.7, 128.7, 128.6, 128.5,
28.5, 128.5, 128.2, 128.2, 126.0, 125.9, 125.9, 122.8, 71.1, 20.7. HRMS ESI (m/z):
+
calcd for C H N O S [M + H] : 465.1631, found: 465.1636.
2
9
25
2
2
1
,2-diphenyl-4-(phenyl(tosyl)methyl)-1H-imidazole 4ca (66%).
−
1
−1 1
Yellow oil. 61.3 mg. IR (cm ): 3056, 3034, 1515, 1501, 1311, 1132, 616 cm . H
NMR (400 MHz, CDCl ) δ 7.62 (s, 1H), 7.57-7.52 (m, 4H), 7.42-7.38 (m, 3H),
3
7
.32-7.27 (m, 4H), 7.26-7.25 (m, 1H), 7.24-7.17 (m, 7H), 5.62 (s, 1H), 2.38 (s, 3H).
1
3
C {1H} NMR (100 MHz, CDCl ) δ 146.2, 144.4, 138.1, 135.1, 133.9, 132.4, 130.5,
3
1
30.5, 129.6, 129.6, 129.6, 129.4, 129.4, 129.2, 129.2, 128.7, 128.7, 128.7, 128.7,
128.5, 128.5, 128.5, 128.2, 128.2, 125.9, 125.9, 122.7, 71.8, 21.7. HRMS ESI (m/z):
+
calcd for C H N O S [M + H] : 465.1631, found: 465.1633.
2
9
25
2
2
4
-(((3-fluorophenyl)sulfonyl)(phenyl)methyl)-1,2-diphenyl-1H-imidazole 4da
(80%).
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−1 1
Yellow oil. 74.9 mg. IR (cm ): 3035, 3015, 1554, 1507, 1310, 1144, 698 cm . H
NMR (400 MHz, CDCl ) δ 7.59-7.55 (m, 3H), 7.51-7.49(m, 1H), 7.43-7.35 (m, 6H),
3
13
7
.32-7.30 (m, 3H), 7.25-7.23 (m, 3H), 7.22-7.18 (m, 4H), 5.63 (s, 1H). C {1H}
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
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7
8
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1
2
3
4
5
6
7
8
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0
1
2
3
4
5
6
7
8
9
0
NMR (100 MHz, CDCl ) δ 162.06 (d, J = 251.5 Hz), 146.5, 140.1, 140.1, 138.0,
3
1
33.5, 131.8, 130.5, 130.5, 130.33 (d, J = 7.5 Hz), 129.6, 129.6, 129.0, 128.7, 128.7,
128.7, 128.6, 128.6, 128.6, 128.2, 128.2, 125.9, 125.9, 125.21 (d, J = 3.3 Hz), 123.1,
1
20.73 (d, J = 21.2 Hz), 116.83 (d, J = 24.4 Hz), 71.9. HRMS ESI (m/z): calcd for
+
C H FN O S [M + H] : 469.1381, found: 469.1385.
2
8
22
2
2
1
,2-diphenyl-4-(phenyl((3-(trifluoromethyl)phenyl)sulfonyl)methyl)-1H-imidazol
e 4ea (78%).
−1
−1 1
Yellow oil. 80.8 mg. IR (cm ): 3063, 3028, 1550, 1503, 1334, 1133, 773 cm . H
NMR (400 MHz, CDCl ) δ 7.96-7.94 (m, 1H), 7.88 (s, 1H), 7.82-7.76 (m, 1H),
3
1
3
7
.62-7.56 (m, 4H), 7.44-7.31 (m, 7H), 7.25-7.18 (m, 6H), 5.64 (s, 1H). C {1H}
NMR (100 MHz, CDCl ) δ 163.4, 160.9, 148.0, 139.8, 135.6, 130.7, 130.6, 130.6,
3
1
1
30.5, 130.3, 130.3, 129.8, 129.8, 129.8, 129.4, 128.9, 128.9, 128.6, 128.5, 128.3,
28.3, 128.2, 128.2, 128.0, 125.6, 125.29 (q, J = 16.1 Hz), 121.2, 116.6, 67.4. HRMS
+
ESI (m/z): calcd for C H F N O S [M + H] : 519.1349, found: 519.1350.
2
9
22
3
2
2
4
-(((4-methoxyphenyl)sulfonyl)(phenyl)methyl)-1,2-diphenyl-1H-imidazole 4fa
(50%).
−
1
−1
Yellow oil. 48.0 mg. IR (cm ): 3067, 3031, 1547, 1503, 1302, 1140, 1030, 762 cm .
1
H NMR (400 MHz, CDCl ) δ 7.62 (s, 1H), 7.58-7.26 (m, 2H), 7.54-7.51 (m, 2H),
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7.41-7.39(m, 4H), 7.31- 7.28 (m, 4H), 7.24-7.21(m, 5H), 6.86-6.84 (m, 2H), 5.59 (s,
1
3
1
1
H), 3.83 (s, 3H). C {1H} NMR (100 MHz, CDCl ) δ 163.6, 146.2, 138.1, 134.1,
3
32.6, 131.5, 131.5, 130.5, 130.5, 129.7, 129.6, 129.6, 129.5, 128.7, 128.7, 128.7,
1
1
1
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1
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2
2
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2
2
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0
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7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
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7
8
9
0
1
2
3
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7
8
9
0
128.6, 128.5, 128.5, 128.5, 128.2, 128.2, 125.9, 125.9, 122.7, 113.7, 113.7, 71.9, 55.6.
+
HRMS ESI (m/z): calcd for C H N O S [M + H] : 481.1580, found: 481.1582.
2
9
25
2
3
4
-(((4-bromophenyl)sulfonyl)(phenyl)methyl)-1,2-diphenyl-1H-imidazole 4ga
(81%).
−
1
−1 1
Yellow oil. 85.5 mg. IR (cm ): 3063, 3030, 1545, 1501, 1321, 1134, 562 cm . H
NMR (400 MHz, CDCl ) δ 7.59-7.56 (m, 3H), 7.52 (s, 3H), 7.38-7.36 (m, 4H),
3
7
.33-7.29 (m, 3H), 7.25-7.18 (m, 7H), 5.63 (s, 1H). 13C {1H} NMR (100 MHz,
CDCl ) δ 147.2, 146.4, 138.0, 137.1, 133.6, 132.0, 131.8, 131.8, 131.0, 131.0, 130.6,
3
130.6, 129.6, 129.6, 129.0, 128.9, 128.7, 128.7, 128.7, 128.7, 128.7, 128.6, 128.3,
1
28.3, 125.9, 125.9, 123.0, 71.9. HRMS ESI (m/z): calcd for C H BrN O S [M +
28 22 2 2
+
H] : 529.0580, found: 529.0582.
1,2-diphenyl-4-(phenyl((4-(trifluoromethyl)phenyl)sulfonyl)methyl)-1H-imidazol
e 4ha (80%).
−1
−1 1
Yellow oil. 82.9 mg. IR (cm ): 3063, 3032, 1534, 1505, 1334, 1123, 783 cm . H
NMR (400 MHz, CDCl ) δ 7.85-7.83 (m, 2H), 7.70-7.67(m, 2H), 7.61-7.56(m, 3H),
3
7
.46-7.30 (m, 7H), 7.24-7.17 (m, 6H), 5.68 (s, 1H). 13C {1H} NMR (100 MHz,
CDCl ) δ 146.5, 141.8, 137.9, 135.14 (d, J = 8.9 Hz), 135.02 (d, J = 43.0 Hz), 133.4,
3
1
31.6, 130.6, 130.6, 130.1, 130.1, 129.6, 129.6, 129.30 (d, J = 4.5 Hz), 128.9, 128.8,
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128.7, 128.7, 128.6, 128.6, 128.6, 128.3, 128.3, 125.9, 125.58 (q, J = 243.6 Hz), 124.6,
+
1
23.2, 121.9, 71.8. HRMS ESI (m/z): calcd for C H F N O S [M + H] : 519.1349,
2
9
22
3
2
2
found: 519.1352.
0
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0
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4
-(((4-chloro-3-(trifluoromethyl)phenyl)sulfonyl)(phenyl)methyl)-1,2-diphenyl-1
H-imidazole 4ia (72%).
−1
−1 1
Yellow oil. 79.5 mg. IR (cm ): 3063, 3035, 1538, 1507, 1310, 1148, 702 cm . H
NMR (400 MHz, CDCl ) δ 7.89-7.88 (m, 1H), 7.84-7.81 (m, 1H), 7.62- 7.57 (m, 3H),
3
1
3
7
.55 (s, 1H), 7.44-7.34 (m, 7H), 7.24-7.20 (m, 6H), 5.63 (s, 1H). C {1H} NMR (100
MHz, CDCl ) δ 148.2, 138.6, 136.7, 135.4, 133.6, 132.1, 130.6, 130.2, 130.2, 130.00
3
(d, J = 42.8 Hz), 129.84 (d, J = 4.5 Hz), 129.59 (d, J = 7.8 Hz), 129.4, 129.1, 129.0,
1
29.0, 128.7, 128.46 (q, J = 240.6 Hz), 128.2, 128.2, 128.2, 128.2, 128.2, 128.2, 127.9,
+
125.0, 123.0, 120.3, 67.6. HRMS ESI (m/z): calcd for C H F ClN O S [M + H] :
2
9
21
3
2
2
5
53.0959, found: 553.0958.
4
-((cyclopropylsulfonyl)(phenyl)methyl)-1,2-diphenyl-1H-imidazole 4ja (67%).
−
1
−1
Yellow oil. 55.5 mg. IR (cm ): 3063, 3032, 1511, 1480, 1306, 1148, 840, 695 cm .
1
H NMR (400 MHz, CDCl ) δ 7.77-7.75 (m, 2H), 7.52 (s, 1H), 7.43-7.35 (m, 9H),
3
7.29-7.27(m, 1H), 7.25-7.22 (m, 3H), 5.61 (s, 1H), 2.59-2.52 (m, 1H), 1.24-1.16 (m,
1
3
2
1
1
H), 1.00-0.93 (m, 2H). C {1H} NMR (100 MHz, CDCl ) δ 146.4, 138.0, 134.5,
3
32.5, 130.3, 130.3, 129.6, 129.6, 129.6, 128.9, 128.8, 128.8, 128.8, 128.7, 128.7,
28.5, 128.3, 128.3, 125.9, 125.9, 122.7, 69.3, 28.7, 5.5, 5.2. HRMS ESI (m/z): calcd
+
for C H N O S [M + H] : 415.1475, found: 415.1480.
2
5
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,2-diphenyl-4-(phenyl(thiophen-2-ylsulfonyl)methyl)-1H-imidazole 4ka (73%).
−
1
−1 1
Yellow oil. 66.6 mg. IR (cm ): 3043, 3020, 1534, 1499, 1325, 1144, 766 cm . H
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
NMR (400 MHz, CDCl ) δ 7.66 (s, 1H), 7.63-7.58 (m, 3H), 7.49-7.47(m, 1H),
3
7
.44-7.40 (m, 3H), 7.37-7.34(m, 3H), 7.32-7.27 (m, 3H), 7.25-7.20 (m, 4H), 7.05-7.02
1
3
(m, 1H), 5.75 (s, 1H). C {1H} NMR (100 MHz, CDCl ) δ 146.3, 138.8, 138.0,
3
135.5, 134.6, 133.6, 132.1, 130.4, 130.4, 129.9, 129.6, 129.6, 129.0, 128.8, 128.8,
1
28.8, 128.6, 128.6, 128.6, 128.2, 128.2, 127.4, 125.9, 125.9, 122.9, 72.8. HRMS
+
ESI (m/z): calcd for C H N O S [M + H] : 457.1040, found: 457.1040.
2
6
21
2
2 2
4-(((4-ethylphenyl)sulfonyl)(phenyl)methyl)-2-phenyl-1-(p-tolyl)-1H-imidazole
4la (68%).
−1
−1 1
Yellow oil. 66.9 mg. IR (cm ): 3043, 3023, 1522, 1511, 1306, 1140, 829 cm . H
NMR (400 MHz, CDCl ) δ 7.60-7.52 (m, 5H), 7.37-7.28 (m, 4H), 7.27-7.19 (m, 8H),
3
7
.11-7.09(m, 2H), 5.61 (s, 1H), 2.68 (q, J = 7.6 Hz, 2H), 2.40 (s, 3H), 1.22 (t, J = 7.6
1
3
Hz, 3H). C {1H} NMR (100 MHz, CDCl ) δ 150.5, 146.1, 138.5, 135.5, 135.2,
3
1
1
33.7, 132.4, 130.5, 130.5, 130.1, 130.1, 129.7, 129.5, 129.5, 128.7, 128.7, 128.7,
28.6, 128.5, 128.5, 128.1, 128.1, 128.0, 128.0, 125.7, 125.7, 122.9, 71.8, 28.9, 21.2,
+
15.2. HRMS ESI (m/z): calcd for C H N O S [M + H] : 493.1964, found:
3
1
29
2
2
4
93.1964.
1
4
-(4-chlorophenyl)-2-phenyl-4-((phenylsulfonyl)(p-tolyl)methyl)-1H-imidazole
ma (78%).
2
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4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
o
−1
Yellow solid, bp. 108.5-109.1 C. 77.7 mg. IR (cm ): 3036, 3021, 1524, 1507, 1305,
−
1 1
1
7
145, 759 cm . H NMR (400 MHz, CDCl ) δ 7.69-7.66 (m, 2H), 7.58-7.52 (m, 2H),
3
.42-7.37 (m, 5H), 7.36-7.35 (m, 1H), 7.26-7.21 (m, 5H), 7.16-7.09 (m, 4H), 5.58 (s,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
1H), 2.31 (s, 3H). C {1H} NMR (100 MHz, CDCl ) δ 146.3, 138.8, 138.0, 136.6,
3
1
34.3, 134.3, 133.5, 130.3, 130.3, 129.8, 129.8, 129.3, 129.3, 129.2, 129.2, 128.8,
128.8, 128.8, 128.6, 128.6, 128.3, 128.3, 128.2, 127.1, 127.1, 125.9, 122.5, 71.5, 21.2.
+
HRMS ESI (m/z): calcd for C H ClN O S [M + H] : 499.1242, found: 499.1245.
2
9
24
2
2
1
-(4-chlorophenyl)-4-((3,4-dimethylphenyl)(phenylsulfonyl)methyl)-2-phenyl-1H-
imidazole 4na (60%).
−
1
−1 1
Yellow oil. 61.5 mg. IR (cm ): 3039, 3024, 1534, 1511, 1306, 1149, 770 cm . H
NMR (400 MHz, CDCl ) δ 7.70-7.68 (m, 2H), 7.58-7.53 (m, 2H), 7.43-7.36 (m, 5H),
3
7.25-7.22 (m, 6H), 7.16-7.13 (m, 2H), 7.07-7.05 (m, 1H), 5.54 (s, 1H), 2.22 (s, 3H),
1
3
2
1
1
.20 (s, 3H). C {1H} NMR (100 MHz, CDCl ) δ 146.2, 138.2, 137.4, 136.8, 136.6,
3
34.5, 134.3, 133.4, 131.5, 129.8, 129.8, 129.8, 129.4, 129.3, 129.3, 128.8, 128.7,
28.7, 128.5, 128.5, 128.3, 128.3, 128.1, 127.7, 127.1, 127.1, 122.4, 71.5, 19.8, 19.6.
+
HRMS ESI (m/z): calcd for C H ClN O S [M + H] : 513.1398, found: 513.1400.
3
0
26
2
2
1
,2-diphenyl-5-(phenyl(phenylsulfonyl)methyl)-1H-imidazole 5aa (92%).
−
1
−1 1
Yellow oil. 82.8 mg. IR (cm ): 3067, 2987, 1534, 1499, 1325, 1140, 770 cm . H
NMR (400 MHz, CDCl ) δ 7.89 (s, 1H), 7.56-7.53 (m, 3H), 7.45-7.42 (m, 1H),
3
7
6
.39-7.31 (m, 9H), 7.25-7.22 (m, 2H), 7.18-7.11 (m, 3H), 6.83-6.81 (m, 1H),
13
.53-6.51 (d, J = 7.6 Hz, 1H), 4.94 (s, 1H). C {1H} NMR (100 MHz, CDCl ) δ
3
2
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The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
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147.8, 137.6, 135.7, 133.8, 130.7, 130.5, 130.3, 130.3, 129.9, 129.8, 129.7, 129.7,
1
29.5, 129.5, 129.2, 128.8, 128.8, 128.8, 128.8, 128.6, 128.6, 128.2, 128.2, 128.2,
+
1
28.2, 128.1, 126.1, 67.3. HRMS ESI (m/z): calcd for C H N O S [M + H] :
2
8
23
2
2
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
451.1475, found: 451.1480.
1
-phenyl-5-(phenyl(phenylsulfonyl)methyl)-2-(p-tolyl)-1H-imidazole 5ab (82%).
−
1
−1 1
Yellow oil. 76.1 mg. IR (cm ): 3067, 3059, 1503, 1440, 1322, 1152, 829 cm . H
NMR (400 MHz, CDCl ) δ 7.85 (s, 1H), 7.57-7.52 (m, 3H), 7.46-7.42 (m, 1H),
3
7
6
1
.40-7.31 (m, 9H), 7.13-7.11(m, 2H), 6.96-6.94(d, J = 8.0 Hz, 2H), 6.84-6.81 (m, 1H),
1
3
.53-6.51 (m, 1H), 4.94 (s, 1H), 2.23 (s, 3H). C {1H} NMR (100 MHz, CDCl ) δ
3
48.0, 138.5, 137.7, 135.8, 133.8, 130.8, 130.4, 130.3, 130.3, 129.9, 129.7, 129.6,
129.4, 129.4, 129.2, 128.9, 128.9, 128.8, 128.8, 128.8, 128.8, 128.6, 128.1, 128.1,
+
1
4
28.1, 127.0, 125.8, 67.3, 21.2. HRMS ESI (m/z): calcd for C H N O S [M + H] :
2
9
25
2
2
65.1631, found: 465.1636.
2-(4-chlorophenyl)-1-phenyl-5-(phenyl(phenylsulfonyl)methyl)-1H-imidazole 5ac
(90%).
−1
−1 1
Yellow oil. 87.1 mg. IR (cm ): 3067, 3049, 1533, 1446, 1342, 1152, 789 cm . H
NMR (400 MHz, CDCl ) δ 7.87 (s, 1H), 7.55-7.52 (m, 3H), 7.47-7.44 (m, 1H),
3
7
6
.38-7.34 (m, 5H), 7.30-7.28 (m, 4H), 7.18-7.15 (m, 2H), 7.12-7.09 (m, 2H),
.82-6.79 (m, 1H), 6.58-6.54 (m, 1H), 4.92 (s, 1H). 13C {1H} NMR (100 MHz,
CDCl ) δ 146.7, 137.6, 135.4, 134.6, 133.9, 130.7, 130.5, 130.2, 130.2, 130.1, 129.9,
3
1
29.9, 129.4, 129.4, 129.4, 129.4, 129.2, 128.9, 128.9, 128.8, 128.8, 128.5, 128.5,
2
9
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