Synthesis of 3-(1H-benzo[d]imidazol-1-yl)isoindolin-1-one derivatives promoted by EtOH-AcOH solvent system

Article abstract of DOI:10.1016/j.tetlet.2013.03.126

A simple and efficient method for the synthesis of 3-(1H-benzo[d]imidazol- 1-yl)isoindolin-1-one derivatives by a one-pot, three-component condensation reaction of phthalaldehydic acid, primary amine, and 2-mercaptobenzimidazole or 2-hydroxybenzimidazole is described. By using EtOH-AcOH (v/v, 15:1) as the solvent system, the reaction proceeds smoothly to give corresponding products in good yields.

Full text of DOI:10.1016/j.tetlet.2013.03.126

Accepted Manuscript
Synthesis of 3-(1H-benzo[d]imidazol-1-yl)isoindolin-1-one derivatives promo‐
ted by EtOH-AcOH solvent system
Hanyun You, Fanglei Chen, Min Lei, Lihong Hu
PII:
S0040-4039(13)00553-4
DOI:
http://dx.doi.org/10.1016/j.tetlet.2013.03.126
TETL 42756
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
8 January 2013
20 March 2013
28 March 2013
Please cite this article as: You, H., Chen, F., Lei, M., Hu, L., Synthesis of 3-(1H-benzo[d]imidazol-1-yl)isoindolin-1-
one derivatives promoted by EtOH-AcOH solvent system, Tetrahedron Letters (2013), doi: http://dx.doi.org/
0.1016/j.tetlet.2013.03.126
1
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Graphical Abstract
Synthesis of 3-(1H-benzo[d]imidazol-1-
yl)isoindolin-1-one derivatives promoted by
EtOH-AcOH solvent system
Leave this area blank for abstract info.
Hanyun You, Fanglei Chen, Min Lei, Lihong Hu

1
Tetrahedron Letters
journal homepage: www.elsevier.com
Synthesis of 3-(1H-benzo[d]imidazol-1-yl)isoindolin-1-one derivatives promoted by
EtOH-AcOH solvent system
a
b
b,
a, b,
Hanyun You , Fanglei Chen , Min Lei  and Lihong Hu

a
School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, P. R. China
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, P. R. China
b
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A simple and efficient method for the synthesis of 3-(1H-benzo[d]imidazol-1-yl)isoindolin-1-
one derivatives by a one-pot, three-component condensation reaction of phthalaldehydic acid,
primary amine, and 2-mercaptobenzimidazole or 2-hydroxybenzimidazole is described. By
using EtOH-AcOH (v/v, 15:1) as the solvent system, the reaction proceeds smoothly to give
corresponding products in good yields.
Available online
2
009 Elsevier Ltd. All rights reserved.
Keywords:
2
-Mercaptobenzimidazole
Phthalaldehydic acid
Isoindolin-1-one
Multi-component reactions (MCRs)
Green chemistry
Isoindolin-1-one derivatives have been reported to possess
report for the synthesis of 3-(1H-benzo[d]imidazol-1-
yl)isoindolin-1-one derivatives (Scheme 1).
1
diverse pharmacological properties, such as antihypertensive,
2
3
4
antiulcer, anesthetic, antipsychotic, as well as efficacy as
5
Initially, we studied the three-component condensation
reaction of phthalaldehydic acid 1 (3 mmol) with benzylamine 2a
(3.6 mmol), and 2-mercaptobenzimidazole 3a (3 mmol) in 5 mL
EtOH at reflux temperature for 12 h to obtain the desired product
vasodilatory agents. In recent year, the alkaloids containing the
isoindolin-1-one core unit have been received wide attention as
6
they are found to be potent MDM2-p53 interaction inhibitors,
7
and U-II receptor antagonists. Moreover, isoindolin-1-ones are
4
aa in 45% yield. To further improve the yields of this synthetic
also used as the important synthons for the synthesis of various
8
9
approach, various solvents had been applied to promote this
transformation and the results are summarized in Table 1.
drugs and natural products. Therefore, due to the importance of
isoindolin-1-one derivatives, it is of great value to develop simple
and efficient method for the synthesis of the compounds
containing isoindolin-1-one core unit.
As shown in Table 1, the usual organic solvents, such as EtOH,
MeOH, MeCN, THF, DCM, DMF, DMSO, and H O, proved to
2
be ineffective, and low yields (0-45%) of the desired product 4aa
were obtained in these solvents (Table 1, entries 1-8). In our
preliminary studies, we have investigated the multi-component
reaction of 2-cyanobenzaldehyde, amine, and EtOH, using EtOH-
AcOH as the solvent system, to obtain the corresponding 2-
One-pot multi-component reactions (MCRs) by virtue of their
convergence, productivity, facile execution, and high yield have
1
0
attracted considerable attention in recent years. MCRs have
been also considered as one of the most efficient methods to
construct heterocyclic compounds from simple starting materials
13
1
1
substituent-3-alkoxy-isoindolin-1-imine derivatives. Threrfore,
in a single operation. As part of a continuing effort in our
laboratory toward the development of new multi-component
condensation reactions, and the development of mild and
practical protocols for the synthesis of useful heterocyclic
we carried out the reaction of phthalaldehydic acid 1,
benzylamine 2a, and 2-mercaptobenzimidazole 3a in 5 mL
EtOH-AcOH (10:1, v/v) as the solvent at reflux temperature for 4
h. To our surprise, we discovered that the solvent of EtOH-AcOH
was also effective to obtain the product 4aa in 80% yield (Table
1
2
compounds, herein we wish to report that a three-component
condensation reaction can be carried out effectively to obtain 3-
1
, entry 11). In order to improve the reaction efficiency, we
varied the volume ratios of EtOH and AcOH, when a ratio of
5:1 was used, the product 4aa was isolated in the highest yield
84%).
(1H-benzo[d]imidazol-1-yl)isoindolin-1-one
derivatives
in
satisfactory yields using phthalaldehydic acid, primary amine,
and 2-mercaptobenzimidazole or 2-hydroxybenzimidazole as the
starting materials. To the best of our knowledge, this is the first
1
(
—
——


Corresponding author. Tel.: +86-21-2023-1000; fax: +86-21-2023-1965; e-mail: mlei@simm.ac.cn (Lei M.)
Corresponding author. Tel.: +86-21-2023-1000; fax: +86-21-2023-1965; e-mail: lhhu@simm.ac.cn (Hu, L.)

2
Tetrahedron Letters
Moreover, we also carried out the reaction in the presence of
0 mol % Brønsted acids or Lewis acids, such as p-TsOH,
sulfamic acid, ZnCl and Cu(OTf) , as the catalysts in EtOH
2
2
2
under reflux for 12 h. However, only moderate yields (50-60%)
of the desired product 4aa were obtained. Therefore, the best
reaction conditions were obtained by using EtOH- AcOH (15:1,
v/v) as the solvent under reflux temperature.
In order to gauge the scope of these conditions, several amines
and benzimidazole analogues were examined under the
optimized conditions using EtOH-AcOH (v/v, 15:1) as the
1
4,15
solvent system.
The results have been summarized in Table 2,
which clearly indicates the generality and scope of the reaction
with respect to various aryl-alkyl, heteroaryl-alkyl, and alkyl
amines. In all cases studied, the three-component reaction using
aryl-alkyl as starting materials proceeded smoothly to give the
corresponding 4 in good yields. Moreover, moderate yields of the
corresponding products 4 were obtained when using heteroaryl-
alkyl, or alkyl amines as substrates. In order to study the steric
effects on this three-component condensation reaction, amines,
including iso-propylamine 2k, cyclopentylamine 2l, and tert-
butylamine 2n were investigated (Table 2, entries 17, 18, 20).
The results revealed that the reaction could proceed smoothly
when using iso-propylamine 2k and cyclopentylamine 2l as
starting materials to obtained desired product 4kb and 4lb in 58%
and 60% yields, respectively. However, the reaction was sluggish
when using tert-butylamine 2n as substrate, and the desired
product 4nb was not determined by LC-MS. Furthermore, we
also carried out the reaction with aromatic amine under similar
reaction conditions, unfortunately, no products were observed
Scheme 1 The condensation of phthalaldehydic acid 1, primary amine 2,
and 2-mercaptobenzimidazole 3a or 2-hydroxybenzimidazole 3b
a
Table 1. Optimization of the reaction conditions
(
Table 2, entry 19).
b
Entry Solvent
Temp.
Time
(h)
Yield (%)
o
(
C)
1
2
3
4
5
6
7
8
9
1
1
1
1
EtOH
MeOH
MeCN
THF
reflux
reflux
reflux
reflux
reflux
80
12
12
12
12
12
12
12
12
3
45
20
25
30
0
DCM
DMF
Scheme 2 To exam whether the mercapto could be as the nucleophilic
35
35
0
group
DMSO
80
In this three-component reaction, 2-mercaptobenzimidazole
3a or 2-hydroxybenzimidazole 3b were employed to synthesis 3-
1H-benzo[d]imidazol-1-yl)isoindolin-1-one derivatives 4. The
results indicated that both 3a and 3b could react to give
corresponding products. The yields of the products were
somewhat lower when using 2-hydroxybenzimidazole 3b (58–
2
H O
80
(
EtOH-AcOH (3:1, v/v)
EtOH-AcOH (5:1, v/v)
EtOH-AcOH (10:1, v/v)
EtOH-AcOH (15:1, v/v)
EtOH-AcOH (20:1, v/v)
EtOH-AcOH (30:1, v/v)
reflux
reflux
reflux
reflux
reflux
reflux
70
74
80
84
80
55
0
1
2
3
4
3
4
8
8
0%) as a substrate than using 2-mercaptobenzimidazole 3a (74–
8%). Furthermore, we also carried out the reaction of
4
6
phthalaldehydic acid 1, benzylamine 2a, and benzimidazole by
using EtOH- AcOH (15:1, v/v) as the solvent under reflux
temperature. The result showed that this three-component
reaction could not take place, which demonstrated that the 2-
mercapto or 2-hydroxy of benzimidazole were very important for
this three-component reaction.
1
6
a
Reaction conditions: Phthalaldehydic acid 1 (3 mmol), benzylamine 2a (3.6
mmol), and 2-mercaptobenzimidazole 3a ( 3 mmol), solvent (5 mL).
b
Isolated yields.

3
a
Table 2. Synthesis of 3-(1H-benzo[d]imidazol-1-yl)isoindolin-1-one derivatives
b
Entry
R
C
X
Time (h)
Product 4
4aa
4ba
4ca
Yield of 4 (%)
1
2
3
4
5
6
7
8
9
6
H
5
CH
2
2a
SH 3a
SH 3a
SH 3a
SH 3a
SH 3a
SH 3a
SH 3a
SH 3a
SH 3a
SH 3a
OH 3b
OH 3b
OH 3b
OH 3b
OH 3b
OH 3b
OH 3b
OH 3b
OH 3b
OH 3b
4
84
81
86
80
82
88
78
78
74
77
72
70
65
60
78
80
58
60
0
4-ClC
4-FC
4-CH
6
H
4
CH
2
2b
2c
CH
4
H
6 4
CH
2
4
3
OC
H
6 4
2
2d
CH
CH
4
4da
4ea
3,4-(CH
3
O)
2
C
C
6
H
3
2
2
2e
5
3,4-(CH
3
O)
2
H
6 3
CH
2
2f
5
4fa
Pyridin-3-ylmethyl 2g
Furan-2-ylmethyl 2h
3
4ga
4ha
4ia
3
CH
3
CH
2
CH
2
2
2i
3
1
1
1
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
8
9
0
CH
3
CH
2
CH
CH
2
2j
3
4ja
C
H
6 5
CH
4-ClC
3,4-(CH
2
2a
CH
O)
5
4ab
4bb
4fb
6
H
4
2
2b
5
3
2
C
H
6 3
CH
2
CH
2
2f
5
Pyridin-3-ylmethyl 2g
5
4gb
4ib
CH
3
CH
2
CH
2
2
2i
5
CH
3
CH
2
CH
CH
2
2j
5
4jb
(CH
Cyclopentyl 2l
2m
C 2n
)
3 2
CH 2k
5
4kb
4lb
5
C
H
6 5
12
12
4mb
4nb
2
(CH
)
3 3
0
a
Reaction conditions: Phthalaldehydic acid 1 (3 mmol), primary amine 2 (3.6 mmol), and 2-mercaptobenzimidazole 3a or 2-hydroxybenzimidazole 3b ( 3 mmol),
EtOH-AcOH (15:1, v/v), reflux.
b
Isolated yields.
It was well known that mercapto was an important
nucleophilic group in organic chemistry. And the compounds
containing mercapto were used widely as the nucleophilic
1
6
reagents in organic synthesis.
Hence, 1-methyl-2-
mercaptobenzimidazole 5a, 2-mercaptobenzothiazole 5b, and 2-
mercaptobenzoxazole 5c were chosen as the starting materials to
exam whether the mercapto could be as the reaction group to
form corresponding products 6 (Scheme 2). Unfortunately, none
of 5a, 5b or 5c could react to give the product 6.
On the basis of the experimental results, a possible mechanism
for the formation of 3-(1H-benzo[d]imidazol-1-yl)isoindolin-1-
one derivatives 4 is presented in Scheme 3. The initial step in this
reaction is the nucleophilic attack of amine 1 to formyl group to
afford the imine intermediate 7, which subsequently reacts with 3
to form another intermediate 8, and intermediate 8 undergoes an
intramolecular cyclization to give the final product 4.
In conclusion, we have demonstrated a simple and efficient
procedure for the synthesis of 3-(1H-benzo[d]imidazol-1-
yl)isoindolin-1-one derivatives 4 using EtOH-AcOH (v/v, 15:1)
as the solvent system. For all the presented reactions, EtOH-
AcOH solvent was used, which is relatively environmentally
benign and supporting ‗green chemistry‘. Moreover, the simple
experimental procedure combined with the easy workup and
good yields of products are salient features of the presented
method.
Scheme 3 The probable mechanism for the formation of compound 4

4
Tetrahedron
Acknowledgments
This work was supported by the National Natural Science
Foundation of China (grants 30925040, 81102329, 81273397),
the Chinese National Science & Technology Major Project ―Key
New Drug Creation and Manufacturing Program‖ (grants
2
0
1
013ZX09508104, 2012ZX09301001-001, 2011ZX09307-002-
3), and the Science Foundation of Shanghai (grant
2XD1405700).
References and notes
1
2
3
4
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Ferland, J.-M.; Demerson, C. A.; Humber, L. G. Can. J. Chem.
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Lippmann, W. U.S. Patent 4,267,189, 1981; Chem. Abstr. 1981,
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Laboratori Baldacci, S. P. A. Japanese Patent 5,946,268, 1984;
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(a) Zhuang, Z.-P.; Kung, M.-P.; Mu, M.; Kung, H. F. J. Med.
Chem. 1998, 41, 157. (b) Norman, M. H.; Minick, D. J.; Rigdon,
G. C. J. Med. Chem. 1996, 39, 149.
1
9
5
6
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Achinami, K.; Ashizawa, N.; Kobayasui, F. Japanese Patent
0
3,133,955, 1991; Chem. Abstr. 1991, 115, 255977j.
(a) Hardcastle, I. R.; Ahmed, S. U.; Atkins, H.; Farnie, G.;
Golding, B. T.; Griffin, R. J.; Guyenne, S.; Hutton, C.; Källblad,
P.; Kemp, S. J.; Kitching, M. S.; Newell, D. R.; Norbedo, S.;
Northen, J. S.; Reid, R. J. Saravanan, K.; Willems, H. M. G.;
Lunec, H. J. Med. Chem. 2006, 49, 6209. (b) Hardcastle, I. R.;
Liu, J.; Valeur, E.; Watson, A.; Ahmed, S. U.; Blackburn, T. J.;
Bennaceur, K.; Clegg, W.; Drummond, C.; Endicott, J. A.;
Golding, B. T.; Griffin, R. J.; Gruber, J.; Haggerty, K.;
Harrington, R. W.; Hutton, C.; Kemp, S.; Lu, X.; McDonnell, J.
M.; Newell, D. R.; Noble, M. E. M.; Payne, S. L.; Revill, C. H.;
Riedinger, C.; Xu, Q.; Lunec, J. J. Med. Chem. 2011, 54, 1233.
Lawson, E. C.; Luci, D. K.; Ghosh, S.; Kinney, W. A.; Reynolds,
C. H.; Qi, J.; Smith, C. E.; Wang, Y.; Minor, L. K.; Haertlein, B.
J.; Parry, T. J.; Damiano B. P.; Maryanoff, B. E. J. Med. Chem.
7
8
9
.
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2
009, 52, 7432.
(a) Abramovitch, R. A.; Shinkai, I.; Mavunkel, B. J.; More, K. M.;
O‘Connor, S.; Ooi, G. H.; Pennington, W. T.; Srinivason, P. C.;
Stowers, J. R. Tetrahedron 1996, 52, 3339. (d) Pigeon, P.;
Decroix, B. Tetrahedron Lett. 1997, 38, 2985.
(a) Heaney, H.; Shuhaibar, K. F. Synlett 1995, 47. (b) Othman, M.;
Pigeon, P.; Decroix, B. Tetrahedron 1997, 53, 2495. (c) Boger, D.
L.; Lee, J. K.; Goldberg, J.; Jin, Q. J. Org. Chem. 2000, 65, 1467.
(d) Comins, D. L.; Schilling, S.; Zhang, Y. Org. Lett. 2005, 7, 95.
1
1
1
0. (a) Liu, J.; Lei, M.; Hu, L. Green Chem. 2012, 14, 840. (b)
Alizadeh, A.; Rostamnia, S.; Hu, M.-L. Synlett 2006, 1592. (c)
Zhao, L.; Cheng, G.; Hu, Y. Tetrahedron Lett. 2008, 49, 7364.
1. (a) Bagley, M. K.; Lubinu, M. C. Synthesis, 2006,1283. (b)
Debache, A.; Amimour, M.; Belfaitah, A.; Rhouati, S.; Carboni,
B. Tetrahedron Lett. 2008, 49, 6119.
2. (a) Liu, J.; Lei, M.; Hu, L. Green Chem. 2012, 14, 2534. (b) Zhao,
K.; Lei, M.; Ma, L.; Hu, L. Monatsh. Chem. 2011, 142, 1169 (c)
Xiao, Z.; Lei, M.; Hu, L. Tetrahedron Lett. 2011, 52, 7099.
3. Shen, S.; Xu, X.; Lei, M.; Hu, L. Synthesis 2012, 3543.
4. General procedure for the synthesis of compounds 4aa-4ja: A
mixture of phthalaldehydic acid 1 (3 mmol), amine 2 (3.6 mmol),
and 2-mercaptobenzimidazole 3a (3 mmol) in EtOH-AcOH (5
mL, v/v, 15:1) was refluxed for 3-5 h. After completion of the
reaction (TLC), the solid was filtered off, washed with water and
further purified by recrystallisation from ethanol (5 mL) to yield
pure products 4aa-4ja.
1
1
1
1
5. General procedure for the synthesis of compounds 4ab-4lb: A
mixture of phthalaldehydic acid 1 (3 mmol), amine 2 (3.6 mmol),
and hydroxybenzimidazole 3b (3 mmol) in EtOH-AcOH (5 mL,
v/v, 15:1) was refluxed for 5 h. After completion of the reaction
(TLC), the solvent was removed under reduced pressure and the
crude product was purified by column chromatography to afford
the corresponding products 4ab-4lb.
6. (a) Xia, Z.; Lv, X.; Wang, W.; Wang, X. Tetrahedron Lett. 2011,
5
2, 4906. (b) Tomioka, K.; Okuda, M.; Nishimura, K.; Manabe,
S.; Kanai, M.; Nagaoka, Y.; Koga, K. Tetrahedron Lett. 1998, 39,
141.
2

Supporting Information
Synthesis of 3-(1H-benzo[d]imidazol-1-yl)isoindolin-1-one derivatives
promoted by EtOH-AcOH solvent system
a
b
b,
a, b,
Hanyun You, Fanglei Chen, Min Lei, * Lihong Hu,
*
a
School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, P.
R. China
b
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, P. R. China
Fax: +86(21)20231965
E-mail: mlei@simm.ac.cn (Lei M.); lhhu@simm.ac.cn (Hu L.)
1

Table of Contents
General information .............................................................................................................. 1
General procedure for the synthesis of compounds 4aa-4ja.................................................. 1
General procedure for the synthesis of compounds 4ab-4lb ................................................. 1
Analytical data for compound 4 ............................................................................................ 2
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
13
H, C NMR, and LC-MS of compound 4aa...................................................................... 11
13
H, C NMR, and LC-MS of compound 4ba...................................................................... 13
13
H, C NMR, and LC-MS of compound 4ca...................................................................... 15
13
H, C NMR, and LC-MS of compound 4da...................................................................... 17
13
H, C NMR, and LC-MS of compound 4ea...................................................................... 19
13
H, C NMR, and LC-MS of compound 4fa ...................................................................... 21
13
H, C NMR, and LC-MS of compound 4ga...................................................................... 23
13
H, C NMR, and LC-MS of compound 4ha...................................................................... 25
13
H, C NMR, and LC-MS of compound 4ia....................................................................... 27
13
H, C NMR, and LC-MS of compound 4ja....................................................................... 29
13
H, C NMR, and LC-MS of compound 4ab...................................................................... 31
13
H, C NMR, and LC-MS of compound 4bb ..................................................................... 33
13
H, C NMR, and LC-MS of compound 4fb...................................................................... 35
13
H, C NMR, and LC-MS of compound 4gb ..................................................................... 37
13
H, C NMR, and LC-MS of compound 4ib ...................................................................... 39
13
H, C NMR, and LC-MS of compound 4jb ...................................................................... 41
13
H, C NMR, and LC-MS of compound 4kb ..................................................................... 43
13
H, C NMR, and LC-MS of compound 4lb ...................................................................... 45
1

General information
Melting points were measured by a WRS-1B micromelting point apparatus and are uncorrected.
NMR spectra were recorded on a Bruker AMX 400 instrument or Bruker AMX 500 instrument
using solvent peaks as DMSO-d solutions. HRESIMS were determined on a Micromass Q-Tof
6
Global mass spectrometer and ESIMS were run on a Bruker Esquire 3000 Plus Spectrometer. TLC
was performed on GF254 silica gel plates (Yantai Huiyou Inc., China).
General procedure for the synthesis of compounds 4aa-4ja
A
mixture of phthalaldehydic acid
1
(3 mmol) ， amine
2
(3.6 mmol), and
2
-mercaptobenzimidazole 3a (3 mmol) in EtOH-AcOH (5 mL, v/v, 15:1) was refluxed for 3-5 h.
After completion of the reaction (TLC), the solid was filtered off, washed with water and further
purified by recrystallisation from ethanol (5 mL) to yield pure products 4aa-4ja.
General procedure for the synthesis of compounds 4ab-4lb
1

A mixture of phthalaldehydic acid 1 (3 mmol)，amine 2 (3.6 mmol), and hydroxybenzimidazole 3b
(
3 mmol) in EtOH-AcOH (5 mL, v/v, 15:1) was refluxed for 5 h. After completion of the reaction
TLC), the solvent was removed under reduced pressure and the crude product was purified by
(
column chromatography to afford the corresponding products 4ab-4lb.
Analytical data for compound 4
2-Benzyl-3-(2-mercapto-1H-benzo[d]imidazol-1-yl)isoindolin-1-one (4aa):
o
1
White solid; Mp: 282.0–282.7 C; H NMR (400 MHz, DMSO-d ): δ = 4.52 (d, J = 15.2 Hz, 1 H),
6
4
7
.61 (d, J = 15.2 Hz, 1 H), 5.83 (d, J = 8.1 Hz, 1 H), 6.78 (t, J = 7.7 Hz, 1 H), 6.98–7.14 (m, 7 H),
.41 (d, J = 7.3 Hz, 1 H), 7.64 (t, J = 7.3 Hz, 1 H), 7.70 (t, J = 7.3 Hz, 1 H), 7.82 (s, 1 H), 7.97 (d,
13
J = 7.3 Hz, 1 H), 13.09 (s, 1 H); C NMR (100 MHz, DMSO-d ): δ = 44.6, 69.0, 109.6, 110.6,
6
1
1
3
22.8, 123.7, 123.8, 124.1, 127.5, 128.0, 128.3, 120.0, 131.0, 131.3, 132.3, 133.6, 136.6, 140.7,
–
+
67.3, 170.4; MS (ESI): m/z 370 ([M – H] ); HRMS (ESI) calcd for C H N OS [M + H]
2
2
17
3
72.1092, found 372.1080.
2-(4-Chlorobenzyl)-3-(2-mercapto-1H-benzo[d]imidazol-1-yl)isoindolin-1-one (4ba):
o
1
White solid; Mp: 243.4–244.5 C; H NMR (400 MHz, DMSO-d ): δ = 4.51 (d, J = 15.3 Hz, 1 H),
6
4
7
.62 (d, J = 15.3 Hz, 1 H), 5.77 (d, J = 8.0 Hz, 1 H), 6.77 (t, J = 6.9 Hz, 1 H), 6.98–7.04 (m, 4 H),
.09 (d, J = 8.2 Hz, 2 H), 7.41 (d, J = 7.3 Hz, 1 H), 7.63 (t, J = 7.3 Hz, 1 H), 7.70 (t, J = 7.3 Hz, 1
2

1
3
H), 7.83 (s, 1 H), 7.97 (d, J = 7.3 Hz, 1 H), 13.07 (s, 1 H); C NMR (100 MHz, DMSO-d ): δ =
6
4
1
3.9, 69.0, 109.6, 110.6, 122.8, 123.7, 123.8, 124.2, 128.2, 129.7, 129.9, 131.0, 131.2, 132.1,
–
32.2, 133.6, 135.6, 140.6, 167.3, 170.4; MS (ESI): m/z 404 ([M – H] ); HRMS (ESI) calcd for
+
C H ClN OS [M + H] 406.0775, found 406.0762.
2
2
17
3
2-(4-Fluorobenzyl)-3-(2-mercapto-1H-benzo[d]imidazol-1-yl)isoindolin-1-one (4ca):
o
1
White solid; Mp: 256.3–256.8 C; H NMR (400 MHz, DMSO-d ): δ = 4.53 (d, J = 17.2 Hz, 1 H),
6
4
7
7
6
1
.62 (d, J = 17.2 Hz, 1 H), 5.78 (d, J = 8.1 Hz, 1 H), 6.74–6.82 (m, 3 H), 6.97–7.05 (m, 2 H),
.11–7.15 (m, 2 H), 7.41 (d, J = 7.4 Hz, 1 H), 7.63 (t, J = 7.4 Hz, 1 H), 7.69 (t, J = 7.4 Hz, 1 H),
1
3
.83 (s, 1 H), 7.97 (d, J = 7.4 Hz, 1 H), 13.08 (s, 1 H); C NMR (100 MHz, DMSO-d ): δ = 43.9,
6
2
9.0, 109.5, 110.5, 114.9 and 115.0 ( J = 17.0 Hz), 122.7, 123.7, 123.8, 124.1, 129.9, 129.9 and
CF
3
4
30.0 ( J = 7.0 Hz), 130.9, 131.2, 132.2, 132.8 and 132.8 ( J = 2.0 Hz), 133.6, 140.6, 160.6
CF
CF
1
–
and 162.6 ( J = 193.0 Hz), 167.2, 170.4; MS (ESI): m/z 388 ([M – H] ); HRMS (ESI) calcd for
CF
+
C H FN OS [M + H] 390.1071, found 390.1083.
2
2
17
3
3-(2-Mercapto-1H-benzo[d]imidazol-1-yl)-2-(4-methoxybenzyl)isoindolin-1-one (4da):
o
1
White solid; Mp: 222.7–226.1 C; H NMR (400 MHz, CDCl ): δ = 3.66 (s, 3 H), 4.63 (d, J = 14.8
3
Hz, 1 H), 4.71 (d, J = 14.8 Hz, 1 H), 6.08 (d, J = 8.2 Hz, 1 H), 6.54 (t, J = 8.6 Hz, 2 H), 6.81 (t, J
=
7.8 Hz, 1 H), 7.06 (t, J = 8.8 Hz, 1 H), 7.14 (d, J = 7.8 Hz, 1 H), 7.22 (d, J = 8.6 Hz, 2 H), 7.43
(dd, J = 7.6, 1.0 Hz, 1 H), 7.56 (td, J = 7.6, 1.2 Hz, 1 H), 7.64 (t, J = 8.6 Hz, 1 H), 7.89 (s, 1 H),
3

1
3
8
.09 (d, J = 7.6 Hz, 1 H), 13.33 (s, 1 H); C NMR (100 MHz, CDCl ): δ = 44.3, 55.2, 69.3, 110.0,
3
1
1
4
10.5, 113.4, 123.1, 123.5, 123.7, 124.3, 127.9, 129.7, 130.0, 130.3, 130.4, 132.3, 132.9, 140.1,
–
+
58.8, 167.7, 170.0; MS (ESI): m/z 400 ([M – H] ); HRMS (ESI) calcd for C H N O S [M + H]
2
3
20
3
2
02.1271, found 402.1260.
2-(3,4-Dimethoxybenzyl)-3-(2-mercapto-1H-benzo[d]imidazol-1-yl)isoindolin-1-one (4ea):
o
1
White solid; Mp: 221.5–222.2 C; H NMR (400 MHz, CDCl ): δ = 3.73 (s, 3 H), 3.79 (s, 3 H),
3
4
1
.65 (d, J = 14.8 Hz, 1 H), 4.70 (d, J = 14.8 Hz, 1 H), 6.09 (d, J = 8.2 Hz, 1 H), 6.51 (d, J = 8.2 Hz,
H), 6.81 (td, J = 8.4, 1.2 Hz, 1 H), 6.87–90 (m, 2 H), 7.06 (t, J = 7.9 Hz, 1 H), 7.14 (d, J = 7.9
Hz, 1 H), 7.42 (d, J = 7.5 Hz, 1 H), 7.56 (td, J = 7.5, 1.2 Hz, 1 H), 7.64 (t, J = 7.5 Hz, 1 H), 7.92 (s,
1
3
1
6
1
H), 8.10 (d, J = 7.5 Hz, 1 H), 11.29 (s, 1 H); C NMR (100 MHz, CDCl ): δ = 44.3, 55.3, 55.4,
3
8.9, 109.4, 109.7, 110.1, 111.2, 120.5, 122.5, 122.9, 123.3, 123.8, 127.8, 129.4, 129.8, 129.9,
–
31.7, 132.4, 139.6, 147.6, 147.8, 167.3, 169.6; MS (ESI): m/z 430 ([M – H] ); HRMS (ESI) calcd
+
for C H N O S [M + H] 432.1376, found 432.1366.
2
4
22
3
3
2-(3,4-Dimethoxyphenethyl)-3-(2-mercapto-1H-benzo[d]imidazol-1-yl)isoindolin-1-one (4fa):
o
1
White solid; Mp: 231.3–232.8 C; H NMR (400 MHz, DMSO-d ): δ = 2.65–2.73 (m, 1 H),
6
2.84–2.93 (m, 1 H), 3.09–3.17 (m, 1 H), 3.65 (s, 3 H), 3.69 (s, 3 H), 3.87–3.95 (m, 1 H), 5.84 (d, J
=
8.1 Hz, 1 H), 6.61 (d, J = 8.0 Hz, 1 H), 6.69 (d, J = 8.1 Hz, 1 H), 6.76 (s, 1 H), 6.83 (t, J = 7.7
Hz, 1 H), 7.08 (t, J = 7.7 Hz, 1 H), 7.20 (d, J = 7.7 Hz, 1 H), 7.40 (d, J = 7.3 Hz, 1 H), 7.60 (t, J =
4

7.3 Hz, 1 H), 7.66 (t, J = 7.0 Hz, 1 H), 7.80 (s, 1 H), 7.90 (d, J = 7.3 Hz, 1 H), 13.32 (brs, 1 H);
1
3
C NMR (100 MHz, DMSO-d ): δ = 33.4, 41.9, 55.7, 55.7, 68.4, 109.5, 110.9, 112.0, 112.5,
6
1
1
4
20.7, 123.0, 123.8, 123.9, 123.9, 129.9, 130.8, 130.9, 131.5, 132.5, 133.3, 140.4, 147.6, 148.9,
–
+
67.1, 170.6; MS (ESI): m/z 444 ([M – H] ); HRMS (ESI) calcd for C H N O S [M + H]
2
5
24
3
3
46.1533, found 446.1541.
3-(2-Mercapto-1H-benzo[d]imidazol-1-yl)-2-(pyridin-3-ylmethyl)isoindolin-1-one (4ga):
o
1
White solid; Mp: 291.3–291.6 C; H NMR (400 MHz, DMSO-d ): δ = 4.56 (d, J = 15.4 Hz, 1 H),
6
4
7
7
.69 (d, J = 15.4 Hz, 1 H), 5.77 (d, J = 8.1 Hz, 1 H), 6.76 (t, J = 7.0 Hz, 1 H), 6.93–7.04 (m, 3 H),
.40–7.46 (m, 2 H), 7.64 (t, J = 7.2 Hz, 1 H), 7.70 (t, J = 7.4 Hz, 1 H), 7.86 (s, 1 H), 7.98 (d, J =
1
3
.4 Hz, 1 H), 8.18 (d, J = 3.5 Hz, 1 H), 8.32 (brs, 1 H), 13.11 (s, 1 H); C NMR (100 MHz,
DMSO-d ): δ = 42.3, 69.1, 109.5, 110.6, 122.8, 123.2, 123.8, 123.9, 124.2, 129.8, 131.0, 131.2,
6
–
1
3
32.1, 132.2, 133.6, 135.6, 140.6, 148.7, 149.1, 167.4, 170.4; MS (ESI): m/z 371 ([M – H] );
+
+
73 ([M + H] ); HRMS (ESI) calcd for C H N OS [M + H] 373.1118, found 373.1129.
2
1
17
4
2-(Furan-2-ylmethyl)-3-(2-mercapto-1H-benzo[d]imidazol-1-yl)isoindolin-1-one (4ha):
o
1
White solid; Mp: 291.6–293.1 C; H NMR (400 MHz, DMSO-d ): δ = 4.58 (d, J = 16.6 Hz, 1 H),
6
4
1
7
6
.63 (d, J = 16.6 Hz, 1 H), 5.86 (d, J = 8.2 Hz, 1 H), 6.06 (s, 1 H), 6.10 (s, 1 H), 6.78 (t, J = 7.8 Hz,
H), 7.03 (t, J = 7.8 Hz, 1 H), 7.08–7.15 (m, 2 H), 7.40 (d, J = 7.4 Hz, 1 H), 7.60–7.69 (m, 2 H),
1
3
.83 (s, 1 H), 7.94 (d, J = 7.4 Hz, 1 H), 13.16 (s, 1 H); C NMR (100 MHz, DMSO-d ): δ = 37.7,
6
9.0, 108.2, 109.4, 110.4, 110.5, 122.7, 123.7, 123.8, 124.1, 129.9, 130.9, 131.4, 132.0, 133.6,
5

–
1
40.7, 142.7, 149.7, 167.0, 170.5; MS (ESI): m/z 360 ([M – H] ); HRMS (ESI) calcd for
+
C H N O S [M + H] 362.0958, found 362.0950.
2
0
16
3
2
3-(2-Mercapto-1H-benzo[d]imidazol-1-yl)-2-propylisoindolin-1-one (4ia):
o
1
White solid; Mp: 284.7–287.6 C; H NMR (400 MHz, DMSO-d ): δ = 0.73 (t, J = 7.4 Hz, 3 H),
6
1
7
.42–1.53 (m, 2 H), 2.86–2.94 (m, 1 H), 3.54–3.63 (m, 1 H), 5.93 (d, J = 8.1 Hz, 1 H), 6.88 (t, J =
.8 Hz, 1 H), 7.11 (t, J = 7.8 Hz, 1 H), 7.22 (d, J = 7.8 Hz, 1 H), 7.42 (d, J = 7.3 Hz, 1 H), 7.62 (t,
J = 7.3 Hz, 1 H), 7.67 (t, J = 7.3 Hz, 1 H), 7.78 (s, 1 H), 7.92 (d, J = 7.4 Hz, 1 H), 13.28 (s, 1 H);
1
3
C NMR (100 MHz, DMSO-d ): δ = 11.6, 21.4, 41.9, 68.5, 109.5, 110.9, 123.1, 123.8, 123.9,
6
–
1
24.0, 123.0, 130.8, 131.5, 132.5, 133.3, 140.6, 167.2, 170.6; MS (ESI): m/z 322 ([M – H] );
+
HRMS (ESI) calcd for C H N OS [M + H] 324.1165, found 324.1177.
18
18
3
2-Butyl-3-(2-mercapto-1H-benzo[d]imidazol-1-yl)isoindolin-1-one (4ja):
o
1
White solid; Mp: 242.7–243.4 C; H NMR (400 MHz, DMSO-d ): δ = 0.72 (t, J = 7.3 Hz, 3 H),
6
1.05–1.21 (m, 2 H), 1.38–1.47 (m, 2 H), 2.90–2.99 (m, 1 H), 3.58–3.66 (m, 1 H), 5.93 (d, J = 8.1
Hz, 1 H), 6.88 (t, J = 8.0 Hz, 1 H), 7.11 (t, J = 8.0 Hz, 1 H), 7.22 (d, J = 8.0 Hz, 1 H), 7.42 (d, J =
7
1
.3 Hz, 1 H), 7.62 (t, J = 7.3 Hz, 1 H), 7.67 (t, J = 7.3 Hz, 1 H), 7.78 (s, 1 H), 7.91 (d, J = 7.3 Hz,
13
H), 13.29 (s, 1 H); C NMR (100 MHz, DMSO-d ): δ = 13.9, 19.8, 30.0, 39.9, 68.5, 109.5,
6
110.9, 123.1, 123.7, 123.9, 124.0, 130.0, 130.8, 131.5, 132.5, 133.3, 140.6, 167.2, 170.6; MS
–
+
(
ESI): m/z 336 ([M – H] ); HRMS (ESI) calcd for C H N OS [M + H] 338.1322, found
19 20 3
338.1318.
6

2-Benzyl-3-(2-hydroxy-1H-benzo[d]imidazol-1-yl)isoindolin-1-one (4ab):
o
1
White solid; Mp: 216.0–216.2 C; H NMR (400 MHz, CDCl ): δ = 4.47 (d, J = 15.4 Hz, 1 H),
3
4
7
7
.89 (d, J = 15.4 Hz, 1 H), 5.89 (d, J = 8.0 Hz, 1 H), 6.71–6.75 (m, 1 H), 6.96–7.03 (m, 3 H),
.12–7.15 (m, 3 H), 7.29–7.33 (m, 2 H), 7.44 (d, J = 7.5 Hz, 1 H), 7.59 (td, J = 7.5, 1.0 Hz, 1 H),
1
3
.66 (t, J = 7.5 Hz, 1 H), 8.09 (d, J = 7.5 Hz, 1 H), 10.17 (s, 1 H); C NMR (100 MHz, CDCl ): δ
3
=
44.4, 65.9, 109.8, 109.9, 121.7, 122.4, 123.5, 124.2, 127.0, 127.5, 127.9, 128.3, 128.4, 130.3,
–
1
32.4, 132.8, 135.9, 140.2, 155.8, 167.6; MS (ESI): m/z 354 ([M – H] ); HRMS (ESI) calcd for
+
C H N O [M + H] 356.1394, found 356.1381.
2
2
18
3
2
2-(4-Chlorobenzyl)-3-(2-hydroxy-1H-benzo[d]imidazol-1-yl)isoindolin-1-one (4bb):
o
1
White solid; Mp: 202.3–203.2 C; H NMR (400 MHz, CDCl ): δ = 4.59 (d, J = 15.1 Hz, 1 H),
3
4.73 (d, J = 15.1 Hz, 1 H), 5.79 (d, J = 8.0 Hz, 1 H), 6.70–6.74 (m, 1 H), 6.97–7.00 (m, 3 H), 7.04
(d, J = 8.4 Hz, 2 H), 7.20 (d, J = 8.4 Hz, 2 H), 7.45 (d, J = 7.5 Hz, 1 H), 7.61 (td, J = 7.5, 1.2 Hz, 1
1
3
H), 7.67 (t, J = 7.5 Hz, 1 H), 8.08 (d, J = 7.5 Hz, 1 H), 9.67 (s, 1 H); C NMR (100 MHz, CDCl ):
3
δ = 43.9, 66.0, 109.7, 109.9, 121.8, 122.5, 123.5, 124.3, 126.9, 127.6, 128.3, 129.6, 130.4, 132.2,
–
1
32.9, 133.4, 134.4, 140.0, 155.6, 167.5; MS (ESI): m/z 388 ([M – H] ); HRMS (ESI) calcd for
+
C H ClN O [M + H] 390.1004, found 389.9892.
2
2
17
3
2
7

2-(3,4-Dimethoxyphenethyl)-3-(2-hydroxy-1H-benzo[d]imidazol-1-yl)isoindolin-1-one (4fb):
o
1
White solid; Mp: 212.3–212.5 C; H NMR (400 MHz, CDCl ): δ = 2.83–2.91 (m, 1 H),
3
2
.99–3.06 (m, 1 H), 3.30–3.37 (m, 1 H), 3.77 (s, 3 H), 3.80 (s, 3 H), 4.04–4.12 (m, 1 H), 5.82 (d, J
8.0 Hz, 1 H), 6.58 (d, J = 8.2 Hz, 1 H), 6.70–6.76 (m, 3 H), 6.95 (s, 1 H), 7.01 (td, J = 7.7, 1.0
Hz, 1 H), 7.12 (d, J = 7.7 Hz, 1 H), 7.41 (d, J = 7.5 Hz, 1 H), 7.57 (td, J = 7.5, 1.2 Hz, 1 H), 7.64 (t,
=
1
3
J = 7.5 Hz, 1 H), 8.03 (d, J = 7.5 Hz, 1 H), 10.11 (s, 1 H); C NMR (100 MHz, CDCl ): δ = 33.7,
3
4
1
1.9, 55.7, 55.7, 66.0, 109.9, 109.9, 111.0, 111.6, 120.7, 121.9, 122.5, 123.4, 124.0, 127.0, 127.8,
–
30.3, 130.7, 132.6, 132.7, 139.9, 147.4, 148.7, 155.8, 167.6; MS (ESI): m/z 428 ([M – H] );
+
HRMS (ESI) calcd for C H N O [M + H] 430.1761, found 430.1755.
25
24
3
4
3-(2-Hydroxy-1H-benzo[d]imidazol-1-yl)-2-(pyridin-2-ylmethyl)isoindolin-1-one (4gb):
o
1
White solid; Mp: 254.5–255.4 C; H NMR (400 MHz, CDCl ): δ = 4.74 (d, J = 15.6 Hz, 1 H),
3
4
.94 (d, J = 15.6 Hz, 1 H), 5.82 (d, J = 8.0 Hz, 1 H), 6.65–6.70 (m, 1 H), 6.90–7.00 (m, 3 H), 7.13
s, 1 H), 7.20 (d, J = 7.8 Hz, 1 H), 7.41 (td, J = 7.8, 1.8 Hz, 1 H), 7.45 (t, J = 7.4 Hz, 1 H), 7.60 (td,
J = 7.4, 1.2 Hz, 1 H), 7.65 (t, J = 7.4 Hz, 1 H), 8.08 (d, J = 7.4 Hz, 1 H), 8.33 (d, J = 4.9 Hz, 1 H),
(
1
3
9
1
.78 (s, 1 H); C NMR (100 MHz, CDCl ): δ = 46.1, 66.5, 109.6, 109.8, 121.5, 122.2, 122.2,
3
22.2, 123.5, 124.3, 127.0, 127.8, 130.2, 132.3, 132.8, 136.3, 140.4, 149.1, 155.6, 155.8, 167.7;
–
+
MS (ESI): m/z 355 ([M – H] ); HRMS (ESI) calcd for C H N O [M + H] 356.1273, found
2
1
16
4
2
356.1279.
8

3-(2-Hydroxy-1H-benzo[d]imidazol-1-yl)-2-propylisoindolin-1-one (4ib):
o
1
White solid; Mp: 273.1–273.3 C; H NMR (400 MHz, CDCl ): δ = 0.91 (t, J = 7.4 Hz, 3 H),
3
1.59–1.73 (m, 2 H), 2.98–3.05 (m, 1 H), 3.76–3.84 (m, 1 H), 5.93 (d, J = 7.9 Hz, 1 H), 6.76 (td, J
=
7.9, 1.1 Hz, 1 H), 7.01–7.05 (m, 2 H), 7.13 (d, J = 7.5 Hz, 1 H), 7.45 (d, J = 7.4 Hz, 1 H), 7.58
1
3
(
td, J = 7.4, 1.3 Hz, 1 H), 7.64 (t, J = 7.4 Hz, 1 H), 8.04 (d, J = 7.4 Hz, 1 H), 9.73 (s, 1 H); C
NMR (100 MHz, CDCl ): δ = 11.4, 21.3, 41.6, 65.6, 109.9, 109.9, 122.0, 122.5, 123.3, 124.0,
3
–
1
27.0, 127.8, 130.2, 132.5, 132.7, 140.0, 155.7, 167.6; MS (ESI): m/z 306 ([M – H] ); HRMS (ESI)
+
calcd for C H N O [M + H] 308.1394, found 308.1387.
18
18
3
2
2-Butyl-3-(2-hydroxy-1H-benzo[d]imidazol-1-yl)isoindolin-1-one (4jb):
o
1
White solid; Mp: 243.8–244.2 C; H NMR (400 MHz, CDCl ): δ = 0.88 (t, J = 7.3 Hz, 3 H),
3
1.29–1.39 (m, 2 H), 1.58–1.66 (m, 2 H), 3.00–3.07 (m, 1 H), 3.82–3.89 (m, 1 H), 5.93 (d, J = 8.0
Hz, 1 H), 6.76 (td, J = 8.0, 1.0 Hz, 1 H), 7.01–7.05 (m, 2 H), 7.15 (d, J = 7.7 Hz, 1 H), 7.45 (d, J =
7
1
1
.6 Hz, 1 H), 7.58 (td, J = 7.5, 1.3 Hz, 1 H), 7.64 (t, J = 7.5 Hz, 1 H), 8.04 (d, J = 7.4 Hz, 1 H),
13
0.12 (s, 1 H); C NMR (100 MHz, CDCl ): δ = 13.7, 20.1, 30.0, 39.7, 65.6, 109.9, 109.9, 121.9,
3
22.5, 123.3, 124.0, 127.0, 127.8, 130.2, 132.5, 132.7, 140.1, 155.8, 167.6; MS (ESI): m/z 320
–
+
(
[M – H] ); HRMS (ESI) calcd for C H N O [M + H] 322.1550, found 322.1558.
19 20 3 2
9

3-(2-Hydroxy-1H-benzo[d]imidazol-1-yl)-2-isopropylisoindolin-1-one (4kb):
o
1
White solid; Mp: 261.1–261.9 C; H NMR (400 MHz, CDCl ): δ = 1.03 (d, J = 7.0 Hz, 3 H), 1.45
3
(d, J = 7.0 Hz, 3 H), 4.48–4.55 (m, 1 H), 6.04 (d, J = 8.0 Hz, 1 H), 6.78 (t, J = 7.9 Hz, 1 H), 7.02 (t,
J = 7.7 Hz, 1 H), 7.10 (s, 1 H), 7.15 (d, J = 7.8 Hz, 1 H), 7.40 (d, J = 7.4 Hz, 1 H), 7.56 (t, J = 7.4
1
3
Hz, 1 H), 7.61 (t, J = 7.4 Hz, 1 H), 8.01 (d, J = 7.4 Hz, 1 H), 10. 16 (s, 1 H); C NMR (100 MHz,
CDCl ): δ = 19.8, 19.8, 43.6, 64.1, 109.4, 109.6, 121.4, 121.9, 122.6, 123.3, 126.6, 127.3, 129.7,
3
–
1
32.1, 132.2, 140.0, 154.9, 167.2; MS (ESI): m/z 306 ([M – H] ); HRMS (ESI) calcd for
+
C H N O [M + H] 308.1394, found 308.1390.
1
8
18
3
2
2-Cyclopentyl-3-(2-hydroxy-1H-benzo[d]imidazol-1-yl)isoindolin-1-one (4lb):
o
1
White solid; Mp: 228.1–228.6 C; H NMR (400 MHz, CDCl ): δ = 1.48–1.58 (m, 3 H),
3
1
.62–1.66 (m, 1 H), 1.74–1.84 (m, 3 H), 2.03–2.08 (m, 1 H), 4.32–4.40 (m, 1 H), 6.09 (d, J = 8.0
Hz, 1 H), 6.79 (t, J = 8.0 Hz, 1 H), 7.03 (t, J = 7.7 Hz, 1 H), 7.10 (s, 1 H), 7.15 (d, J = 7.7 Hz, 1 H),
.39 (d, J = 7.3 Hz, 1 H), 7.55 (td, J = 7.5, 1.2 Hz, 1 H), 7.60 (t, J = 7.4 Hz, 1 H), 8.00 (d, J = 7.4
7
13
Hz, 1 H), 10. 16 (s, 1 H); C NMR (100 MHz, CDCl ): δ = 23.8, 23.9, 29.0, 29.1, 54.1, 65.7,
3
109.9, 110.1, 122.0, 122.4, 123.0, 123.7, 127.1, 127.8, 130.2, 132.6, 132.9, 140.4, 155.4, 168.0;
–
+
MS (ESI): m/z 332 ([M – H] ); HRMS (ESI) calcd for C H N O [M + H] 334.1550, found
1
8
18
3
3
334.1540.
10

1
13
H, C NMR, and LC-MS of compound 4aa
11

12

1
13
H, C NMR, and LC-MS of compound 4ba
13

14

1
13
H, C NMR, and LC-MS of compound 4ca
15

16

1
13
H, C NMR, and LC-MS of compound 4da
17

18

1
13
H, C NMR, and LC-MS of compound 4ea
19

20

1
13
H, C NMR, and LC-MS of compound 4fa
21

22