Facile synthesis of chiral benzimidazolium salts and the application in asymmetric catalytic borylation

Article abstract of DOI:10.3987/COM-16-13434

A synthetic method towards chiral benzimidazolium salts is developed. The stereocenter is introduced by direct aromatic substitution of 2-fluoronitrobenzene with optically pure amines. After nitro group reduction, selective arylation of the primary amine is achieved via copper catalyzed Chan-Lam coupling reaction. Finally, cyclization of the diamine with HC(OMe)₃ afforded the desired chiral benzimidazolium salts. In situ generated benzimidazole carbenes show potential application for asymmetric catalytic borylation of α,β-unsaturated esters, providing up to 85% ee value with a catalyst loading of only 0.5 mol%.

Full text of DOI:10.3987/COM-16-13434

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HETEROCYCLES, Vol. 92, No. 5, 2016
HETEROCYCLES, Vol. 92, No. 5, 2016, pp. 944 - 953. © 2016 The Japan Institute of Heterocyclic Chemistry
Received, 9th February, 2016, Accepted, 11th March, 2016, Published online, 30th March, 2016
DOI: 10.3987/COM-16-13434
FACILE SYNTHESIS OF CHIRAL BENZIMIDAZOLIUM SALTS AND
THE APPLICATION IN ASYMMETRIC CATALYTIC BORYLATION
Jie Zhou,† Xiaohui Liu,† and Zhihua Sun*
College of Chemistry and Chemical Engineering, Shanghai University of
Engineering Science, 333 Longteng Road, Shanghai 201620, P.R. China
†These authors contributed equally to this work.
*Zhihua Sun, Telephone: +86 21 67791432, Fax: +86 21 67791214, E-mail:
sungaris@gmail.com
Abstract – A synthetic method towards chiral benzimidazolium salts is developed.
The stereocenter is introduced by direct aromatic substitution of
2-fluoronitrobenzene with optically pure amines. After nitro group reduction,
selective arylation of the primary amine is achieved via copper catalyzed
Chan-Lam coupling reaction. Finally, cyclization of the diamine with HC(OMe)3
afforded the desired chiral benzimidazolium salts. In situ generated benzimidazole
carbenes show potential application for asymmetric catalytic borylation of
α,β-unsaturated esters, providing up to 85% ee value with a catalyst loading of
only 0.5 mol%.
Chiral N-heterocyclic carbene (NHC) catalysts were one of the most rapidly developing catalysts in
recent years.1 Those have been widely used in the benzoin condensation reaction,2 Stetter reaction,3
Diels-Alder reaction,4 olefin metathesis reaction5 and hydrogenations.6 The skeleton of N-heterocyclic
carbene precursors are mostly imidazoles, benzimidazoles, triazoles and thiazoles (Figure 1).7
Figure 1. Core structures of classic NHCs
During the past few years, one of our main research interests had been focused on the synthesis and

HETEROCYCLES, Vol. 92, No. 5, 2016
945
application of achiral benzimidazolium salts in organic reactions.7a,8 Based on our recent results that
chiral 6-membered ring N-heterocyclic carbenes performed excellent asymmetric catalytic activity in
borylation of α,β-unsaturated esters,7a we were curious to figure out if it could also be applicable to
structurally more simplified chiral benzimidazole carbenes. However, the development and
diversification of chiral benzimidazolium salts has lagged largely behind that of their imidazolium salts
counterparts.9 Benzimidazolium salts bearing remote stereocenters could be easily accessed by
conjugation of benzimidazolium salts with readily available chiral fragments. Sakaguchi et al.10 had
utilized such kinds of chiral carbene precursors in a series of asymmetric catalytic reactions, including
asymmetric conjugate addition reaction, asymmetric hydrosilylation of ketones and asymmetric
intermolecular boron Heck-type reactions. To the best of our knowledge, currently there are only limited
reports available for the synthesis of benzimidazolium salts equipped with chirality alpha to the nitrogen
atom.11 One synthetic approach to such motif was published from Diver’s group, highlighting on the
palladium catalyzed sequential amination of o-dibromobenzene with chiral amine and another amine or
imine.12 Alternatively, chiral benzimidazoles were approached by sequential substitution of
2-halo-nitrobenzene with chiral amine, reduction of nitro group and cyclization with orthoformate.
Consequently, chiral benzimidazolium salts were merged via intermolecular or intramolecular
N-alkylation with halides.13a,13b In a reversed manner, Mauduit’s group functionalized the amino group by
reductive amination prior to the ring closure, to generate similar molecular scaffold.13c Although with
available procedures to access benzimidazolium salts with alpha chirality, application of these classes of
carbene precursors in asymmetric catalytic reaction was scarce as well and usually provided inferior
enantioselectivity or diastereoselectivity.12c,13 A novel species of axial chiral benzimidazolium salts
combining the structure of biphenyl or binaphthyl group with benzimidazolium scaffold is an exception.
Developed by Shi’s group, they found much more prevalent applications in various asymmetric reactions
and offered excellent enantioselectivity.14 However, it leads to dispute that the induction effect may
derive from the axial chirality from naphthyl group, while not that of C1-symmetric stereocenter from
benzimidazolium salts. Concerning the rareness of chiral benzimidazole carbenes, especially their limited
application in asymmetric catalysis, in this article, we report an alternative method for the generation of
chiral benzimidazolium salts with a wide variety of substitution diversity, and exploring their behavior in
enantioselective borylation.
A traditional synthesis of achiral benzimidazolium salts relied on Buchwald-Hartwig coupling of
o-phenylenediamine with two equivalents of halides, followed by ring closure with orthoester.8d The
extensive development of Buchwald-Hartwig coupling reaction in recent years has enabled the
monoarylation of o-phenylenediamine to be easily accessed.15 We envisioned that the chirality could be
introduced to the resultant primary amine, via a serial of operations including condensation with cheap

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HETEROCYCLES, Vol. 92, No. 5, 2016
optically active ketones from chiral pool, and then substrate controlled diastereoselective reduction.
Controlled monoarylation of o-phenylenediamine was realized by mixing equal molar ratio of amine and
aryl halide under general Buchwald-Hartwig coupling condition. With the combination of Pd2(dba)3 and
BINAP (Scheme 1), compounds 2a-b were obtained in 63-65% yield by applying t-BuONa as the base.
Compounds 2a-b were then condensed with d-camphor to generate ketimines 3a-b under the catalysis of
TiCl4. 3a-b were not stable towards silica gel and should be directly transferred to reduction without
further purification. The reduction with sodium borohydride went uneventful and provided compounds
4a-b as single diastereoisomer. Finally, the desired chiral benzimidazole carbene precursors 5a-b were
forged by cyclization of 4a-b with HC(OMe)3 under acidic condition in 66-70% yield. However, when
l-menthone was condensed with 2a-b to generate 3c-d, the reduction of 3c-d yielded 4c as a pair of
diastereoisomers with the ratio of nearly 2:1. It could presumably be reasoned by epimerization of the
isopropyl group via imine-enamine tautomerization of 3c-d.16 While in the case of 3a-b, tautomerization
induced racemization was not possible due to the intrinsic characteristics of quaternary carbon center. 4d
was not stable towards silica gel.
chiral ketone
DCM,TEA
TiCl4, reflux
H
BINAP, Pd2(dba)3
toluene, t-BuONa
H
N R1
N R1
NH2
NH2
R2*
N
63-65%
NH2
3a-d
1
2a: R1= 2,4,6-trimethylbenzyl
2b: R1= 2-naphthyl
R1
N+
H
N R1
DCM, NaBH4, 0 oC
63-76% for 2 steps
HC(OMe)3, HCl
66-70%
Cl-
R2*
N
R2*
5a-b
N
H
4a: R1= 2,4,6-trimethylbenzyl, R2* from d-camphor
4b: R1= 2-naphthyl, R2* from d-camphor
4c: R1= 2,4,6-trimethylbenzyl, R2* from l-menthone
4d: R1= 2-naphthyl, R2* from l-methone
N
N
Cl-
Cl-
N
N
5b
5a
Scheme 1. Synthetic route for chiral benzimidazole NHC precursors

HETEROCYCLES, Vol. 92, No. 5, 2016
947
Since the protocol was not applicable to α-monosubstituted ketone, we then resorted to another strategy
for assembling the chiral benzimidazolium salts with similar scaffold (Scheme 2). In a reversed manner,
we planned to install the chiral amine at the very beginning. Thus, o-fluoronitrobenzene was heated with
o
commercial available optically active amines in DMF at 90 C.17 The reaction proceeded smoothly with
K2CO3 as the base, offering chiral nitrobenzylamines 7a-c in 62-64% yield. Then the nitro group of 7a-c
was reduced with lithium aluminum hydride, Pd/C-H2 or iron powder, respectively. Different from
Mauduit’s protocol,13c which functionalized the primary amine by reductive amination with aldehyde, we
planned to attach aryl group to the nitrogen atom. Surprisingly, selective arylation of the primary amino
group of 8a-c was not feasible under conventional Buchwald-Hartwig reaction condition, leaving the
starting material intact, presumably due to deactivation of palladium catalyst by substrate chelation. To
our delight, the same transformation was realized with Chan-Lam coupling condition,18 using Cu(OAc)2
as the catalyst. It is well known that copper catalyzed Chan-Lam cross coupling reaction is especially
suitable for selective amide or aryl amine over alkyl amine or alcohol, thus also circumventing the
regioselectivity problem in substrates 8a-c. With triethylamine serving as the base, 9a and 9b were
obtained in 62-68% yield. Slightly differently, no reaction occurred with 8c under the same condition.
However, while switching the base from triethylamine to buffer system of K2CO3 and benzoic acid,19 9c
was assembled in similar yield. The cyclization of 9a-c with HC(OMe)3 furnished chiral
benzimidazolium salts in 61%-72% yield.
H
H
K2CO3, DMF,
90 oC, 4 h
N R3*
N R3*
F
reduction
71-79%
NO2
NH2
62-64%
NO2
7a: R3* from (S)-methyl 2-amino-3-phenylpropanoate
7b: R3* from 1-amino-2-hydroxyindane
7c: R3* from cyclohexanediamine
6
8a-c
R3*
N+
H
Cu(OAc)2, base
DCM, rt
N R3*
HC(OMe)3, HCl
61-72%
Cl-
N
R4
62-68%
N R4
H
9a-c
5c-e
N
NO2
Cl-
N
N
N
N
Cl-
Cl-
NH2
N
HO
HO
5c
5d
5e
Scheme 2. Synthetic route for chiral benzimidazole NHC precursors

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HETEROCYCLES, Vol. 92, No. 5, 2016
In summary, we report a facile synthesis of chiral benzimidazole NHC precursors from
2-fluoronitrobenzene in four steps. Aromatic substitution of 2-fluoronitrobenzene with optically active
amine allows smooth introduction of the chiral center. After reduction of the nitro group, selective
arylation of primary amine is feasible by Chan-Lam coupling reaction with copper catalyst. Condensation
of the diamine with HC(OMe)3 furnished the chiral benzimidazolium salts. NHCs 5b generated in situ
from these precursors shows good asymmetric catalytic properties for borylation of α, β-unsaturated ester
with enantioselectivity of up to 85% with a catalyst loading of only 0.5 mol% (Table 1).7a The successful
application of chiral benzimidazole carbenes in asymmetric catalytic borylation broadens the possibility
of their usage in more classes of enantioselective reaction. We are currently screening more chiral
benzimidazole carbenes for better asymmetric induction. These results would be reported in due course.
Table 1. Examples of asymmetric borylation
O
BPin O
B2Pin2 (1.1 eq), 5b (0.5 mol%),
CuCl (1 mol%), -35 oC
R2
R2
R1
R1
THF, t-BuONa (20 mol%), MeOH (1 eq)
D1-D3
C1-C3
Isolated yield
(%)
Entry
R1
R2
Product
eea (%)
1
2
3
trifluoromethyl
4-methyl
4-Cl
methoxy
methoxy
methoxy
D1
D2
D3
87
89
86
85
79
74
aEnantiomeric excess: determined by HPLC analysis using a CHIRALPAK® column.
EXPERIMENTAL
1H NMR and 13C NMR spectra were recorded in CDCl3 operating at 400 MHz and 100 MHz. Proton
chemical shifts are reported relative to the residual proton signals of the deuterated solvent CDCl3 (7.26
ppm) or DMSO-d6 (2.50 and 3.33 ppm) or TMS. Carbon chemical shifts were internally referenced to the
deuterated solvent signals in CDCl3 (77.00 ppm) or DMSO-d6 (40.0 ppm). Data are represented as
follows: chemical shift, multiplicity (br = broad singlet, s = singlet, d = doublet, t = triplet, m = multiplet),
coupling constant in Hertz (Hz), and integration. Products were identified by comparison to spectral data
reported in the literature. Mass spectra (both at low resolution and at high resolution) were recorded on a
time-of-flight mass spectrometer with an ESI source. High performance liquid chromatography (HPLC)
was performed using a chromatograph equipped with a Chiral pak column (250 mm × 4.6 mm) with
hexane/i-PrOH as the eluent.

HETEROCYCLES, Vol. 92, No. 5, 2016
949
Typical procedure for synthesis of 8a-c:
(S)-2-((2-Aminophenyl)amino)-3-phenylpropan-1-ol (8a): The crude product 7a (2 g, 6.7 mmol) was
o
dissolved in anhydrous THF (100 mL) in a 250 mL round-bottomed flask and cooled to -20 C. Then,
lithium aluminum hydride (8.0 mL, 8.0 mmol) was added in batches. Then, the reaction mixture was
stirred at rt for about 2 h. After completion of the reaction (checked by TLC), the reaction mixture was
quenched with saturated NaCl solution, extracted with DCM and dried with Na2SO4. The crude product
was purified by silica gel chromatography (hexane: EtOAc =15: 1 to 10:1) to give 1.1 g 8a; brown oil,
yield 71%; 1H NMR (400 MHz, CDCl3) δ 7.30-7.38 (m, 2H), 7.23-7.25 (m, 3H), 6.78-6.90 (m, 2H), 6.75
(d, J = 3.5 Hz, 2H), 3.70-3.78 (m, 2H), 3.53-3.57 (m, 1H), 2.97-3.08 (m, 2H).
(1R, 2S)-1-((2-Aminophenyl)amino)-2,3-dihydro-1H-inden-2-ol (8b): The crude product 7b (2 g, 7.4
mmol) was dissolved in anhydrous MeOH (50 mL) in a sealed tube and Pd/C was added. Then, the
reaction mixture was stirred at rt for about 2 h under H2. After completion of the reaction (checked by
TLC), the resulting suspension was filtered through a plug of Celite (diatomaceous earth), and the filter
cake was washed with MeOH. MeOH was removed under vacuum. The crude product was purified by
1
silica gel chromatography (hexane: EtOAc =15: 1 to 10:1) to give 1.1 g 8b; brown oil, yield 64%; H
NMR (400 MHz, CDCl3) δ 7.40 (d, J = 7.0 Hz, 1H), 7.22-7.37 (m, 3H), 6.87-7.03 (m, 2H), 6.74-6.86 (m,
13
2H), 4.90 (d, J = 4.6 Hz, 1H), 4.73 (t, J = 4.1 Hz, 1H), 3.21 (dd, J = 16.6, 5.0 Hz, 2H), 3.09 (s, 1H); C
NMR (100 MHz, CDCl3) δ 141.8, 140.6, 137.0, 134.3, 128.3, 127.1, 125.5, 124.2, 121.2, 119.9, 117.7,
113.6, 72.3, 63.0, 39.6. MS (ESI-TOF) m/z: 241.1 [M+H]+.
tert-Butyl ((1R,2R)-2-((2-aminophenyl)amino)cyclohexyl)carbamate (8c): The crude product 7c (2 g,
6.0 mmol) was dissolved in EtOH: H2O (1:1, 50 mL) in a 100 mL round-bottomed flask and iron powder
(1.7 g, 29.81 mmol). Then, the reaction mixture was heated to reflux. After completion of the reaction
(checked by TLC), the resulting suspension was filtered through a plug of Celite (diatomaceous earth),
and washed with EtOH. Then, EtOH was removed under vacuum and the water layer was extracted with
DCM. The crude product was used for the next step directly without further purification.
Typical procedure for synthesis of 9a-c:
(S)-3-Phenyl-2-((2-(phenylamino)phenyl)amino)propan-1-ol (9a): A mixture of diamine 8a (0.50 g,
2.06 mmol), phenylboronic acid (0.52 g, 4.33 mmol) was dissolved in DCM (20-30 mL) in a 100 mL
round-bottomed flask equipped with a stir bar. Then, Et3N (0.42 g, 4.12 mmol) and Cu(OAc)2·H2O (0.21
g, 1.03 mmol) were added to it respectively at room temperature. They would be stirred overnight under
the condition of air atmosphere. After completion of the reaction (checked by TLC), the mixture was
filtered through Celite and washed with EtOAc. The crude product was purified by silica gel
1
chromatography (hexane:EtOAc = 40:1, 20:1 or 5:1) to give 0.41 g 9a; brown oil, yield 62%; H NMR

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HETEROCYCLES, Vol. 92, No. 5, 2016
(400 MHz, CDCl3) δ 7.20-7.27 (m, 5H), 7.12-7.17 (m, 4H), 6.86 (dd, J = 14.8, 7.5 Hz, 1H), 6.76 (t, J =
7.2 Hz, 1H), 6.71 (d, J = 7.7 Hz, 1H), 3.78-3.81 (m, 1H), 3.72 (dd, J = 11.0, 4.2 Hz, 1H), 3.51 (dd, J =
13
11.0, 5.6 Hz, 1H), 2.80-2.94 (m, 2H). C NMR (100 MHz, CDCl3) δ 145.8, 143.0, 137.9, 129.3, 129.0,
128.9, 128.5, 126.5, 126.3, 125.7, 119.4, 118.1, 115.2, 112.5, 63.4, 56.1, 37.7.MS (ESI-TOF) m/z: 319.2
[M+H]+.
(1R,2S)-1-((2-((2-Nitrophenyl)amino)phenyl)amino)-2,3-dihydro-1H-inden-2-ol (9b): brown oil,
1
yield 63%; H NMR (400 MHz, CDCl3) δ 9.11 (s, 1H), 8.23 (d, J = 8.8 Hz, 1H), 7.29-7.38 (m, 2H),
7.16-7.30 (m, 4H), 7.12 (dd, J = 16.4, 7.8 Hz, 2H), 6.91 (t, J = 7.6 Hz, 1H), 6.79 (dd, J = 5.0, 3.6 Hz, 2H),
4.95 (d, J = 4.2 Hz, 1H), 4.73 (d, J = 4.6 Hz, 1H), 3.20 (dd, J = 16.7, 4.6 Hz, 1H), 3.04 (d, J = 16.7 Hz,
1H). 13C NMR (100 MHz, CDCl3) δ 144.4, 144.2, 141.0, 140.3, 136.0, 133.1, 129.0, 128.6, 128.5, 127.3,
126.7, 125.6, 124.4, 123.9, 118.9, 117.5, 116.0, 112.8, 72.4, 62.8, 39.6. MS (ESI-TOF) m/z: 362.1
[M+H]+.
tert-Butyl ((1R,2R)-2-((2-(phenylamino)phenyl)amino)cyclohexyl)carbamate (9c): A mixture of
diamine 8c (0.50 g, 1.64 mmol), phenylboronic acid (0.42 g, 3.1 mmol) was dissolved in DCM (20-30
mL) in a 100 mL round-bottomed flask equipped with a stir bar. Then, K2CO3 (0.23 g, 1.64 mmol),
benzoic acid (0.10 g, 0.82 mmol) and Cu(OAc)2·H2O (0.16 g, 0.33 mmol) were added to it respectively at
o
room temperature. They would be stirred at 80 C for 4 h under the condition of air atmosphere. After
completion of the reaction (checked by TLC), the mixture was filtered through Celite and washed with
EtOAc. The crude product was purified by silica gel chromatography (hexane:EtOAc = 40:1, 20:1 or 5:1)
to give 0.42 g 9c. pale yellow oil, yield 68%; 1H NMR (400 MHz, CDCl3) δ 7.21 (t, J = 7.7 Hz, 3H), 7.04
(t, J = 7.7 Hz, 1H), 6.82 (dd, J = 14.3, 7.4 Hz, 3H), 6.59-6.77 (m, 2H), 4.53 (br, 1H), 3.47 (br, 1H), 3.12
(br, 1H), 2.25 (d, J = 13.3 Hz, 1H), 2.09 (dd, J = 11.4, 4.3 Hz, 1H), 1.75 (s, 2H), 1.38 (s, 9H), 1.23-1.34
(m, 4H), 1.04-1.25 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 156.5, 145.6, 129.1, 125.0, 123.8, 119.1,
115.6, 79.5, 54.4, 32.9, 32.2, 29.7, 28.3, 24.9, 24.5. MS (ESI-TOF) m/z: 382.2 [M+H]+.
Typical procedure for synthesis of 5a-e:
1-Mesityl-3-((1R,2S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)-1H-benzo[d]imidazol-3-ium chloride
(5a): Compound 4a (0.050 mg, 0.14 mmol) was dissolved in trimethyl orthoformate (5 mL). Then,
concentrated hydrochloric acid (0.1 mL) was added. The mixture was reacted at room temperature for 12
h. Then most solvent was evaporated under reduced pressure. The crude product was purified by silica gel
chromatography (DCM: MeOH = 10:1) to give 37 mg 5a; white solid, yield 66%, mp 206.3-206.8 oC; 1H
NMR (400 MHz, DMSO-d6) δ 10.41 (s, 1H), 8.18-8.49 (m, 1H), 7.79 (t, J = 7.7 Hz, 1H), 7.70 (t, J = 7.7
Hz, 1H), 7.42 (d, J = 8.2 Hz, 1H), 7.27 (d, J = 7.2 Hz, 2H), 4.85-5.10 (m, 1H), 2.67 (d, J = 13.2 Hz, 1H),
2.41 (d, J = 4.9 Hz, 3H), 2.24 (dd, J = 13.3, 9.4 Hz, 1H), 1.94-2.09 (m, 5H), 1.92 (d, J = 13.1 Hz, 3H),

HETEROCYCLES, Vol. 92, No. 5, 2016
951
13
1.66-1.86 (m, 2H), 1.32-1.46 (m, 1H), 1.18 (s, 1H), 0.99 (s, 3H), 0.90 (s, 3H), 0.79 (s, 2H); C NMR
(100 MHz DMSO-d6) δ 142.6, 141.4, 135.8, 135.5, 133.1, 130.2, 130.1, 127.5, 116.3, 113.6, 66.1, 51.0,
48.4, 44.8, 36.0, 26.7, 21.4, 21.2, 19.9, 17.5. MS (ESI-TOF) m/z: 373.3 [M+H]+. HRMS (ESI-TOF) calcd
for C26H33N2 [M]+ 373.2638, Found: 373.2641.
+
1-(Naphthalen-2-yl)-3-((1R,2S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)-1H-benzo[d]imidazol-3-
o
1
ium chloride (5b): white solid, yield 67%, mp 168.3-170.2 C; H NMR (400 MHz, DMSO-d6) δ 10.41
(s, 1H), 8.46 (s, 1H), 8.29 (dd, J = 24.0, 8.5 Hz, 2H), 8.16 (d, J = 4.9 Hz, 2H), 7.91 (dd, J = 14.3, 9.2 Hz,
2H), 7.63-7.85 (m, 4H), 4.94 (t, J = 7.8 Hz, 1H), 2.78-2.81 (m, 1H), 2.21 (dd, J = 13.1, 9.5 Hz, 1H), 2.03
(s, 1H), 1.66-1.94 (m, 3H), 1.42 (s, 1H), 1.08 (s, 3H), 0.92 (t, J = 9.0 Hz, 6H); 13C NMR (100 MHz,
DMSO-d6) 142.1, 133.6, 133.4, 133.1, 132.0, 130.5, 128.9, 128.5, 128.1, 127.3, 125.6, 123.7, 115.9,
114.1, 66.2, 51.1, 48.4, 44.9, 36.5, 36.0, 26.8, 21.5, 20.3, 12.8. MS (ESI-TOF) m/z: 381.2 [M+H]+.
HRMS (ESI-TOF) calcd for C26H33N2 [M]+ 381.2325, Found: 381.2323.
+
(S)-3-(1-Hydroxy-3-phenylpropan-2-yl)-1-phenyl-1H-benzo[d]imidazol-3-ium chloride (5c): brown
solid, yield 72%; mp 147.2-148.7 oC; 1H NMR (400 MHz, DMSO-d6) δ 10.45 (s, 1H), 8.21 (d, J = 7.8 Hz,
1H), 7.62-7.92 (m, 8H), 7.34 (d, J = 7.3 Hz, 2H), 7.27 (t, J = 7.5 Hz, 2H), 7.18 (t, J = 7.3 Hz, 1H), 5.47 (t,
J = 6.0 Hz, 1H), 5.36 (br, 1H), 3.77-4.05 (m, 2H), 3.49 (d, J = 7.2 Hz, 1H); 13C NMR (100 MHz,
DMSO-d6) δ 142.1, 137.0, 134.5, 133.5, 132.1, 131.3, 131.1, 130.9, 129.5, 129.0, 128.0, 127.4, 127.3,
125.8, 114.8, 113.9. MS (ESI-TOF) m/z: 329.2 [M+H]+. HRMS (ESI-TOF) calcd for C22H21ClN2O+ [M]+
329.1648, Found: 329.1649.
3-((1R,2S)-2-Hydroxy-2,3-dihydro-1H-inden-1-yl)-1-(2-nitrophenyl)-1H-benzo[d]imidazol-3-ium
chloride (5d): white solid, yield 71%; mp 137.5-139.8 oC; 1H NMR (400 MHz, DMSO-d6) δ 9.95 (s, 1H),
8.50 (s, 1H), 8.25 (d, J = 33.6 Hz, 1H), 8.03-8.13 (m, 3H), 7.75 (dd, J = 23.3, 15.7 Hz, 2H), 7.64 (d, J =
8.2 Hz, 1H), 7.39-7.57 (m, 3H), 7.35 (t, J = 7.2 Hz, 1H), 6.71 (s, 1H), 5.74-5.98 (m, 1H), 4.86 (s, 1H),
3.31 (d, J = 5.1 Hz, 1H), 3.11 (d, J = 16.3 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ 144.7, 144.2, 142.4,
139.9, 136.4, 133.3, 132.2, 131.4, 130.0, 128.2, 127.9, 127.4, 127.1, 126.5, 126.2, 126.5, 126.2, 125.0,
115.1, 113.6. MS (ESI-TOF) m/z: 372.2 [M+H]+. HRMS (ESI-TOF) calcd for C22H18N3O3 [M]+
+
372.1343, Found: 372.1341.
3-((1R,2R)-2-Aminocyclohexyl)-1-phenyl-1H-benzo[d]imidazol-3-ium chloride (5e): white solid,
yield 61%; mp 108.3-109.6 oC; 1H NMR (400 MHz, DMSO-d6) δ 10.44 (s, 1H), 8.38 (d, J = 7.8 Hz, 1H),
7.88-7.93 (m, 2H), 7.82-7.87 (m, 1H), 7.69-7.80 (m, 5H), 4.73 (t, J = 9.3 Hz, 1H), 1.99-2.29 (m, 3H),
1.71-1.95 (m, 2H), 1.38-1.61 (m, 4H); 13C NMR (100 MHz, DMSO-d6) δ 142.1, 133.8, 132.2, 131.6,
130.9, 130.7, 127.8, 127.1, 125.8, 115.2, 113.8, 63.7, 53.9, 34.0, 32.2, 25.1, 24.4. MS (ESI-TOF) m/z:
292.1 [M+H]+. HRMS (ESI-TOF) calcd for C19H22N3 [M]+ 292.1808, Found: 292.1809.
+

952
HETEROCYCLES, Vol. 92, No. 5, 2016
ACKNOWLEDGEMENTS
The authors are grateful for financial support from Shanghai Municipal Education Commission
(No.14ZZ159) and Graduate Innovative Project of Shanghai University of Engineering Science
(No.14KY0402).
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