Palladium-catalyzed annulation of 2-(aryldiazenyl) aniline with dimethyl sulfoxide to access N-aryl-1H-benzo[d]imidazol-1-amine

Article abstract of DOI:10.1016/j.tetlet.2017.08.066

A palladium-catalyzed annulation of 2-(aryldiazenyl) aniline and dimethyl sulfoxide was developed to access N-aryl-1H-benzo[d]imidazol-1-amine in moderate to good yields. Activated by 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct (DABSO), DMSO served as a “[dbnd]CH[sbnd]” fragment during this procedure. It represents a facile pathway leading to benzimidazoles.

Full text of DOI:10.1016/j.tetlet.2017.08.066

Accepted Manuscript
Palladium-Catalyzed Annulation of 2-(Aryldiazenyl) Aniline with Dimethyl
Sulfoxide to Access N-Aryl-1H-benzo[d]imidazol-1-amine
Hepan Wang, Song Sun, Jiang Cheng
PII:
S0040-4039(17)31089-4
DOI:
http://dx.doi.org/10.1016/j.tetlet.2017.08.066
TETL 49256
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
5 July 2017
24 August 2017
28 August 2017
Please cite this article as: Wang, H., Sun, S., Cheng, J., Palladium-Catalyzed Annulation of 2-(Aryldiazenyl) Aniline
with Dimethyl Sulfoxide to Access N-Aryl-1H-benzo[d]imidazol-1-amine, Tetrahedron Letters (2017), doi: http://
dx.doi.org/10.1016/j.tetlet.2017.08.066
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Graphical Abstract
To create your abstract, type over the instructions in the template box below.
Fonts or abstract dimensions should not be changed or altered.
Palladium-Catalyzed Annulation of
2-(Aryldiazenyl) Aniline with
Dimethyl Sulfoxide to Access
N-Aryl-1H-benzo[d]imidazol-1-amine
Hepan Wang, Song Sun, and Jiang Cheng*

1
Tetrahedron Letters
journal homepage: www.els evier.com
Palladium-Catalyzed Annulation of 2-(Aryldiazenyl) Aniline with Dimethyl
Sulfoxide to Access N-Aryl-1H-benzo[d]imidazol-1-amine
Hepan Wang, Song Sun and Jiang Cheng*
aSchool of Petrochemical Engineering, Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, Jiangsu Province Key Laboratory of
Fine Petrochemical Engineering, Changzhou University, Changzhou, 213164, P. R. China.
bCollege of Chemistry & Materials Engineering, Wenzhou University, Wenzhou 325000, P. R. China.
†E-mail: jiangcheng@cczu.edu.cn
ARTICLE INFO
ABSTRACT
Article history:
Received
A palladium-catalyzed annulation of 2-(aryldiazenyl) aniline and dimethyl sulfoxide was
developed to access N-aryl-1H-benzo[d]imidazol-1-amine in moderate to good yields.
Activated by 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct (DABSO), DMSO
served as a “=CH-” fragment during this procedure. It represents a facile pathway leading
to benzimidazoles.
Received in revised form
Accepted
Available online
Keywords:
.
palladium-catalyzed
2-(aryldiazenyl) aniline
activated by DABSO
DMSO served as a “=CH-” fragment
Dimethyl sulfoxide (DMSO) is an aprotic polar solvent1
as well as a versatile reagent in many well-known name
reactions.2-5 Pummerer reaction is one typical example
employing DMSO as a building block in organic synthesis,6
incorporating the fragment of “-CH2SMe” into the final
product.7 After proper activations, DMSO was widely
employed in thiomethylation,8 methylsulfonylation,9
they generally suffer from some limitations, such as the multiple
steps, harsh conditions and availability of functionalized starting
materials. Thus, the development of straightforward and eco-
friendly processes to such frameworks remains highly desirable.
Herein, we wish to report a palladium-catalyzed annulation of 2-
(aryldiazenyl) aniline with DMSO, which serves as a “=CH-”
fragment leading to
(Scheme 1, eq. 4).
N-aryl-1H-benzo[d]imidazol-1-amine
cyanation,10
formylation,11
methylation,12
and
methylenation.13 Besides, DMSO also served as “=CH-”
fragment in sequential annulation/aromatization reaction to
construct heteroaromatic compounds. For example, recently,
Cui developed an unprecedented protocol to access 1,3,5-
triarylbenzenes from chalcones under metal-free and air-
tolerant conditions (Scheme 1, eq. 1).14 Yuan reported the
access of symmetrical and unsymmetrical pyridines whereby
ammonium iodide-promoted cyclization of ketones with
DMSO and ammonium acetate (Scheme 1, eq. 2).15 Ma
demonstrated copper-catalyzed three-component procedure
toward quinozaline involving DMSO (Scheme 1, eq. 3).16
We also demonstrated activation of DMSO by DABSO
Scheme 1. DMSO serving as “=CH-” fragment in the
constuction of heterocycle
(DABSO
=
1,4-diazabicyclo[2.2.2]octane-1,4-diium-1,4-
disulfinate) leading to 4-aryl quinolines.17
Benzimidazoles are ubiquitous motifs in natural products and
biologically active molecules,18 serving as anti-inflammatory,
antimicrobial, antiviral reagents, antitubercular and analgesic.19
Therefore, tremendous efforts have been devoted to access
benzimidazoles, including condensation of benzene-1,2-diamine
with carbonyl compounds synthon20 and transition metal-
catalyzed couplings of ortho-functionalized anilines.21 However,

Tetrahedron
4
Table 1. Screening the optimized reaction conditionsa
Additive
(equiv)
Base
Yield(%)
Entry
Catalyst
NatOBu
<10
23
42
58
68
67
73
65
63
62
--
--
--
1
2
--
KtOBu
--
DABSO (0.5)
DABSO (0.5)
DABSO (0.5)
DABSO (0.5)
DABSO (0.5)
DABSO (0.5)
DABSO (0.5)
DABSO (0.5)
--
--
--
--
--
--
--
--
3
Pd2(dba)3
Pd(dba)2
Pd(PPh3)4
Pd(OAc)2
Pd(CF3COO)2
Pd(acac)2
Pd(PPh3)2Cl2
4
5
6
7
8
9
10
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
DABSO (0.5)
DABCO (0.5)
DABSO (0.2)
DABSO (1.0)
--
--
--
--
--
--
--
--
82, 36b, 65c
11
12
13
14
15
16
17g
17
60
69
0
49d, 64e, 60f
60
DABSO (0.5)
DABSO (0.5)
a
Reaction conditions: substituted 2-(aryldiazenyl) aniline 1 (0.2 mmol),
o
PdCl2 (10 mol%), DABSO (0.5 equiv), in DMSO (3 mL), under N2, 135 C,
a
Reaction conditions: 2-(phenyldiazenyl) aniline 1a (0.2 mmol), Pd (10
mol%), additive (0.5 equiv), in DMSO (3 mL), under N2, 135 oC, 16 h, in
16 h, sealed tube.
b
c
d
e
f
g
sealed tube. Under O2. Under air. 120 oC. 140 oC. 12 h. Reaction
After the establishment of the optimized conditions, this
procedure was applied to access a variety of N-phenyl-1H-
benzo[d]imidazol-1-amine derivatives (Scheme 2). The
procedure tolerated methyl, chloro and fluoro groups in both the
anilinyl and aryl attached in the azo groups, which provided
handles for potentially further functionalizations (3c, 72%; 3g,
53%; 3i, 67% and 3j, 62%). As expected, benzimidazoles were
isolated with yields ranging from 56% to 72% (3b-3j except 3d).
However, the yield of 6-trifluoromethyl-N-phenyl-1H-
benzo[d]imidazol-1-amine 3d decreased significantly to 35%.
Importantly, the diversity of this procedure was further increased
since it allowed the access of N-aryl-1H-benzo[d]imidazol-1-
amine (3k-3r) quickly in moderate to good yields (57-85%).
Once again, the chloro (3m, 77%; 3n, 57%) and bromo (3l, 61%)
groups in the N-aryl survived well under this procedure.
performed on 1.0 mmol scale (1a).
Initially, we tested the reaction of 2-(phenyldiazenyl) aniline
o
1a in DMSO under N2 at 135 C in the presence of NatOBu.
After 16 h, the desired product N-phenyl-1H-benzo[d]imidazol-
1-amine 3a was isolated in less than 10% yield (Table 1, entry 1).
Replacing NatOBu with KtOBu resulted in 23% yield (Table 1,
entry 2). To our delight, the yield dramatically increased to 42%
by using DABSO (0.5 equiv, Table 1, entry 3). Encouraged by
this inspiring result, the reaction efficiency dramatically
increased by using Pd2(dba)3 (58%, Table 1, entry 4). Replacing
Pd2(dba)3 with Pd(dba)2 further increased the reaction efficiency
(68%, Table 1, entry 5). Other catalysts, such as Pd(PPh3)4
(67%)，Pd(OAc)2 (73%)，Pd(CF3COO)2 (65%), Pd(acac)2 (63%)
and Pd(PPh3)2Cl2 (62%) were inferiror to PdCl2 (82%, Table 1,
entries 6-11). Moreover, replacing DABSO with DABCO
resulted significant erosion in the yield of 3a (17%) (Table 1,
entry 12). The reaction became retarded under either O2 (36%) or
air (65%). Changing the loading of DABSO slightly decreased
the yields (Table 1, entries 13 and 14), while it did not work in
the absence of DABSO (Table 1, entry 15). Low yields were
Scheme 3. Preliminary mechanism studies.
o
obtained when the temperature was changed to 120 C (49%) or
140 oC (64%). The yield dropped to 60% with shortened time (12
h, Table 1, entry 16). Importantly, this reaction also could be
conducted on 1 mmol scale to give the desired product 3a in an
acceptable 60% isolated yield (Table 1, entry 17).
Scheme 2. Substrate scope of 2-(aryldiazenyl) aniline.a

3
We thank the National Natural Science Foundation of
To gain some insights into the reaction mechanism, some
control experiments were conducted. First, the reaction could not
be shut down in the presence of 2 equivalents of 2,2,6,6-
tetramethylpiperidinooxy (TEMPO), indicating no radical
pathway was involved (Scheme 3, eq 1). Second, replacing
DMSO with DMSO-d6, N-phenyl-1H-benzo[d]imidazol-2-d-1-
amine was isolated in 78% yield, which not only confimed the
participation of DMSO in such transformation but also provided
a facile pathway to access 2-deuterized analogues (Scheme 3, eq
2). Finally, the presumed intermediate C was not stable enough
to be detected by GC-MS and to be isolated for further
characterizations. However, after the reaction of 2-
(phenyldiazenyl) aniline and chloromethyl methyl sulfide (2
equiv) in toluene, N-phenyl-1H-benzo[d]imidazol-1-amine was
isolated in 20% yield in the presence of PdCl2 (0.1 equiv), along
with the detected CH3SCH2SCH3. This result indicated the
possibility of compound C serving as the intermediate.
China (nos. 21572025, 21372177, 21672028), “Innovation
& Entrepreneurship Talents” Introduction Plan of Jiangsu
Province, the Key University Science Research Project of
Jiangsu Province (15KJA150001), and Advanced Catalysis
and Green Manufacturing Collaborative Innovation Center
for financial supports. Sun thanks the National Natural
Science Foundation of China (no. 21602019) and Young
Natural Science Foundation of Jiangsu Province
(BK20150263) for financial support.
References and notes
1
2
Wu, X.-F; Natte, K. Adv. Synth. Catal. 2016
Corey-Chaykovsky reaction: (a) Corey, E. J.; Chaykovsky, M. J.
Am. Chem. Soc. 1965 87, 1353; (b) Duan, Y. Y.; Zhou, B.; Lin, J.
H.; Xiao, J. C. Chem. Commun. 2015 51, 13127; (c) Hajra, S.;
Aziz, S. M.; Jana, B.; Mahish, P.; Das, D. Org. Lett. 2016 18, 532.
Swern oxidation: (a) Omura, K.; Sharma, A. K.; Swern, D. J. Org.
Chem. 1976 41, 957; (b) Albright, J. D. J. Org. Chem. 1974 39
1977; (c) Oae, S.; Kitao, Y.; Kawamura, S.; Kitaoka, Y.
Tetrahedron. 1963 19, 817; (d) Albright, J. D.; Goldman, L. J.
Am. Chem. Soc. 1967 89, 2416.
Kornblum oxidation: (a) Kornblum, N.; Jones, W. J.; Anderson, G.
J. J. Am. Chem. Soc. 1959 81, 4113; (b) Kornblum, N.; Powers, J.
W.; Anderson, G. J.; Jones, W. J.; Larson, H. O.; Levand, O.;
Weaver, W. M. J. Am. Chem. Soc. 1957 79, 6562.
Pfitzner-Moffatt oxidation: (a) Pfitzner, K. E.; Moffatt, J. G. J. Am.
, 358, 336.
,
,
,
Scheme 4. A tentative mechanism
3
NH2
N
CH3
S
,
,
,
S
H2C
NH
-
N
Ph
O
N
SO2
N
1a
H3C
,
S
S
+
CH2
N
,
N
Ph
O
N
N
O
B
A
C
Pd(II)
-
4
SO2
O
N
S
,
G
N
,
O-
S
Pd(0)
5
6
CH3
S
H3C
S
S
Chem. Soc. 1963
1990, 857.
,
85, 3027; (b) Review: Tidwell, T. T. Synthesis
.
H
C
CH
CH
H
NHPh
B
NHPh
S
S
N
N
HN
N
NH
N
Jones-Mensah, E.; Karki, M.; Magolan, J. Synthesis. 2016, 48
,
CH
N
N
Ph
N
1421.
3a
NHPh
D
F
E
7
8
Bur, S. K.; Padwa, A. Chem. Rev. 2004
Patil, S. M.; Kulkarni, S.; Mascarenhas, M.; Sharma, R.; Roopan,
S. M.; Roychowdhury, A. Tetrahedron. 2013 69, 8255.
Yuan, G.; Zheng, J.; Gao, X.; Li, X.; Huang, L.; Chen, H.; Jiang,
H. Chem. Commun. 2012 48, 7513.
, 104, 2401.
,
Based on these experimental results, a proposed mechanism
was outlined in Scheme 4. Firstly, the activation of DMSO by
DABSO produces intermediate A.22 Then, the deprotonation of
intermediate A provides DABCO oxide G and a thionium ion
intermediate B, which encounters the nucleophillic attack by
substrate 1a leading to intermediate C. After that, intermediate C
is oxidized to iminium ion D by Pd(II).23 Meanwhile, Pd(0) is
produced and was oxidized to Pd(II) by DABCO oxide G.
Subsequently, the intramolecular electron transfer takes place to
produce the cyclized intermediate E, which reacts with B to
access intermediate F.24 Finally, the elimination of
CH3SCH2SCH3 delivers the final product 3a.
9
,
10 Ren, X.; Chen, J.; Chen, F.; Cheng, J. Chem. Commun. 2011, 47,
6725.
11 Fei, H.; Yu, J.; Jiang, Y.; Guo, H.; Cheng, J. Org. Biomol. Chem.
2013 11, 7092.
12 Jiang, X.; Wang, C.; Wei, Y.; Xue, D.; Liu, Z.; Xiao, J. Chem. Eur.
J. 2014 20, 58.
13 Traynelis, V. J.; Hergenrother, W. L. J. Org. Chem. 1964
14 Wang, F.; Shen, J.; Cheng, G.; Cui, X. RSC Adv. 2015 , 73180.
15 Pan, X.; Liu, Q.; Chang, L.; Yuan, G. RSC Adv. 2015 , 51183.
16 Duan, T. T.; Zhai, T.; Liu, H. H.; Yan, Z. L.; Zhao, Y.; Feng, L.;
Ma, C. Org. Biomol. Chem. 2016 14, 6561.
,
,
,
29, 221.
,
5
In conclusion, we have developed a palladium-catalyzed
annulation of 2-(phenyldiazenyl) aniline with dimethyl sulfoxide
toward N-aryl-1H-benzo[d]imidazol-1-amine. DMSO served as a
“=CH-” fragment in this transformation. DABSO played dual
roles in this procedure: one is to activate DMSO; the other is to
oxidize Pd(0) by its oxide. It represents a facile pathway leading
to N-aryl benzimidazoles.
,
5
,
17 Yuan, J.; Yu, J.-T.; Jiang, Y.; Cheng, J. Org. Biomol. Chem. 2017
15, 1334.
,
18 (a) Zhang, Z. B.; Sun, Q. S.; Xia, C. G.; Sun, W. Org. Lett. 2016
,
18, 6316; (b) Prchal, L.; Podlipna, R.; Lamka, J.; Dedkova, T.;
Acknowledgments
Skalova, L.; Vokral, I.; Lecova, L.; Vanek, T.; Szotakova, B.
Environ. Sci. Pollut. Res. 2016, 23, 13015; (c) Townsend, L. B.;

Tetrahedron
, 389; (d) Yadav, G.;
4
Revankar, G. R. Chem. Rev. 1970
Ganguly, S. Eur. J. Med. Chem. 2015
Luxami, V.; Paul, K. RSC Adv. 2014 , 12422; (f) Wu, Q. H.; Li,
Y. P.; Wang, C.; Liu, Z. M.; Zang, X. H.; Zhou, X.; Wang, Z.
Anal. Chim. Acta. 2009 638, 139.
(a) Gao, X.; Yu, B.;. Mei, Q. Q.; Yang, Z. Z.; Zhao, Y.F.; Zhang,
H. Y.; Hao, L. D.; Liu, Z. M. New J. Chem. 2016 40, 8282; (b)
Porcari, A. R.; Devivar, R. V.; Kucera, L. S.; Drach, J. C.;
Townsend, L. B. J. Med. Chem. 1998 2623, 1252; (c) Denny, W.
A.; Rewcastle, G. W.; Baguley, B. C. J. Med. Chem. 1990 33, 814.
20 (a) Deepak, B. N.; Bhalchandra, M. B. Synlett. 2015 26, 2835; (b)
Shainaz, M. L.; Bela, T. Catal. Lett. 2008 122, 338; (c) Pranab, G.;
Amitava, M.; Tetrahedron Lett 2012 53, 6483.
,
70
,
97, 419; (e) Singla, P.;
,
4
,
19
,
,
,
,
,
.
,
21 For selected examples on metal-catalyzed synthesis of 1,2-
disubstituted benzimidazoles, see: (a) Zhu, K. C.; Hao, J. H.;
Zhang, C. P.; Zhang, J. J.; Feng, Y. Q.; Qin, H. L. RSC Adv. 2015
5, 11132; (b) Sun, Z. H.; Bottari, G.; Barta, K. Green Chem. 2015
,
,
17, 5172; (c) Feng, F.; Ye, J.; Cheng, Z.; Xu, X. l.; Zhang, Q. F.;
Ma, L.; Lu, C. S.; Li, X. N. RSC Adv 2016 , 72750.
.
, 6
22 The activation of DMSO by trimethyl(ethyl)amine/SO2 complex
was reported by Olah, where SO2 was oxidized to SO3. See: Olah,
G. A.; VanKar, Y. D.; Arvanaghi, M. Synthesis. 1979, 984.
23 For the Pd(II)-promoted transformation of tertiary amine into
iminium ion, please see: (a) Mane, R. S.; Bhanage, B. M.; J. Org.
Chem. 2016
Jia, M. J. Org. Chem. 2014
L.; Tang, R. Y.; Zhang, X. G.; Li, J. H. Org. Lett. 2011
(d) Sheng, J.; Guo, Y.; Wu, J. Tetrahedron Lett. 2013 69, 6495; (e)
Murahashi, S. I.; Hirano, T.; Yano, T. J. Am. Chem. Soc. 1978
100, 348; (f) Lei, Y.; Wrobleski, A. D.; Golden, J. E.; Powell, D.
R.; Aube, J. J. Am. Chem. Soc. 2005 127, 4552; (g) Bao, Y. S.;
Bao, Z.; Bao, A.; Baiyin, M.; Jia, M. J. Org. Chem. 2014 79, 803.
24 Bates, D. K. J. Org. Chem. 1977 42, 3452.
,
81, 1223; (b). Bao, Y. S,; Zhaorigetu, B.; Baiyin, M.;
79, 803; (c) Liu, Y.; Yao, B.; Deng, C.
13, 2184;
,
,
,
,
,
,
,

5
1. DMSO served as a “=CH-” fragment during
this procedure
2. Activated by 1,4-diazabicyclo[2.2.2]octane
bis(sulfur dioxide) adduct (DABSO)
3. Good yields, good functional group
compatibility.