Benzimidazoles and benzothiazoles from styrenes and N-vinylimidazole via palladium catalysed oxidative C[dbnd]C and C[sbnd]N bond cleavage

Article abstract of DOI:10.1016/j.tetlet.2019.151356

Herein we report a first, palladium catalyzed, one-pot methodology for the synthesis of pharmacologically important benzimidazoles and benzothiazoles from readily available terminal aromatic olefins. The process involves sequential C[dbnd]C/C[sbnd]N bond cleavage followed by C[sbnd]N/C[sbnd]S bond formation.

Full text of DOI:10.1016/j.tetlet.2019.151356

Journal Pre-proofs
Benzimidazoles and Benzothiazoles from Styrenes and N-vinylimidazole via
Palladium Catalysed Oxidative C=C and C-N bond Cleavage
Altab Shaikh, Owk Ravi, S. Pushpa Ragini, Nimma Sadhana, Surendar Reddy
Bathula
PII:
S0040-4039(19)31147-5
DOI:
https://doi.org/10.1016/j.tetlet.2019.151356
TETL 151356
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
14 September 2019
30 October 2019
1 November 2019
Please cite this article as: Shaikh, A., Ravi, O., Pushpa Ragini, S., Sadhana, N., Bathula, S.R., Benzimidazoles and
Benzothiazoles from Styrenes and N-vinylimidazole via Palladium Catalysed Oxidative C=C and C-N bond
Cleavage, Tetrahedron Letters (2019), doi: https://doi.org/10.1016/j.tetlet.2019.151356
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Benzimidazoles and Benzothiazoles from Styrenes and N-vinylimidazole via
Palladium Catalysed Oxidative C=C and C‒N bond Cleavage
a,b
a,b
a,b
a
a,b,
Altab Shaikh, Owk Ravi, Pushpa Ragini S, Nimma Sadhana, Surendar Reddy Bathula
a
Organic Synthesis and Process Chemistry Division CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India
Academy of Scientific and Innovative Research, Ghaziabad - 201 002, India
b
—
——
ARTICLE INFO
ABSTRACT

Corresponding author. Tel.: +0-000-000-0000; fax: +0-000-000-0000; e-mail: author@university.edu
Article history:
Received
Herein we report a first, palladium catalyzed, one-pot methodology for the synthesis of
pharmacologically important benzimidazoles and benzothiazoles from readily available terminal
O
Received in revised form
Accepted
Available online
aromatic olefins. The process involves sequential C=C/C‒N bond cleavage followed by
Ar
X
C−N/C−S bond formation.
Previous work
X = H or OH or Cl
or OR
a)
b)
2009 Elsevier Ltd. All rights reserved.
NH2
X
Ar
X
Ar
X = H or NH2 or OH
XH
N
Keywords: 1) Benzimidazole, 2) C=C bond
Cleavage, 3) Terminal Aromatic Olefins, 4)
Vinylimidazole
R1
R1
X = NH, S
X = NH, S
O
c)
X
Ar
X = CN or COMe or
COOMe or COAr
Our previous work
O
NH2
N
R
d)
+
Ar
Ar
1
. Introduction
Benzimidazoles and benzothiazoles are vital pharmacophoric
NH2
N
R = H, Me, Ph
R2
H
This work
units that correspond to numerous biological activities such as
antiulcer, antimicrobial, anticonvulsant, antiviral and anticancer.1
Benzazol-based marketed drugs such as albendazole,
lansaprazole, mebendazole, telmisartan, astemizole, riluzole,
pramipexole, viozan and ethoxyzolamide further signifies the
pharmaceutical importance of the above privileged structures
X
Ar
e)
N
R1
NH2
Pd(OAc)2 (5 mol%),
AcOH, 90 oC, O2
X = S, NH
R1
N
XH
H
N
N
X = S, NH
R1
Me
N
(
Figure 1). Moreover, these core units are prevalent in various
2
natural products and functional materials. Due to their
widespread applications; considerable efforts have been made
towards the development of efficient methods for the synthesis of
these molecules.
Generally, benzimidazoles and benzothiazoles are synthesized
by the condensation of amino aniline/2-aminothiophenol with
3
4
aldehydes, carboxylic acids and their derivatives (Scheme 1a).
5
6
7a
Alternately, benzylalcohols, benzylamines, methylarenes and
nitroaniline
7
b-7h
have been used as substrates (Scheme 1b). For
instance, Milstein and co-workers reported the synthesis of
benzimidazoles from alcohols and diamines via cobalt catalyzed
dehydrogenative coupling reaction.8 In 2018, Hikawa et al.
reported the construction of 2-arylbenzimidazoles from various
benzyl alcohols.9 Huang et al. reported the cobalt catalyzed
Scheme 1. Synthetic Approaches to Benzimidazole/
Benzothiazole
electrochemical synthesis of
benzazoles from different
1
0
alcohols. Srimani and coworkers reported the synthesis of 2-
substituted and 1,2-disubstituted benzimidazoles by coupling of
diamine with alcohols.11 In addition, Bharate et al. reported metal
free protocol for benzimidazoles from o-phenylenediamine and
benzylamine in ionic liquid medium.12 Luo et al. reported
benzimidazole synthesis from primary amines via by ortho-
quinone catalysis.13 Narender and coworkers reported the
divergent synthesis of benzimidazoles and benzothiazoles from
1
4
15
16
benzylamines. Moreover, β-keto esters, β-keto nitriles and β-
1
7
diketones (Scheme 1c) have also been utilized as substrates for
the synthesis of the title compounds. Likewise, recently, we have

2
Tetrahedron
reported molecular iodine catalyzed oxidative C-C bond
Styrene substituted with deactivating substituents such as 4-
fluorostyrene (3e), 4-bromo (3f) and 3-nitrostyrene (3q)
produced corresponding benzimidazoles in 47%, 44% & 40%
cleavage reaction for the synthesis of benzimidazoles from
acetophenones (Scheme 1d).18 However, use of terminal aromatic
olefins as substrates for synthesis of titled compounds is not
reported. Styrenes are readily available unactivated terminal
alkenes and widely explored in both academia and industry for
the preparation of complex organic molecules. Further, well
2
5
yields under optimized conditions . Next, we have examined the
differently substitued o-phenylenediamines reactivity in this
reaction. Methyl substituted benzene-1,2-diamine reacted well
with 1a to produce 3d in 72% yield. Furthermore, halogen
substrates like 4-flouro, 4-chloro, 4,5 dichloro o-
phenylenediamines furnished the products 3g (49%), 3h (50%)
3o (57%) and 3p (55%) in moderate yields. Furthermore, benzoyl
substituted o-phenylenediamine reacted with simple, 4-methyl
and 4-fluoro substituted styrenes gave desired product in low
yield (Table 2, 3l-3n, 21-27%). Moreover styrenes with electron
donating groups such as 4-methyl and 4-methoxy have produced
corresponding bemzimidazoles (3i-3k) with 4-fluro and 4-chloro
substituted o-Phenylenediamines in good yields (51-57%).
1
9
known reactions of alkenes such as Heck reaction, olefin
hydroformylation,20 Wacker process and olefin metathesis
21
22
ascertain their importance in modern synthetic organic chemistry.
As part of our continuing interest in construction of privileged
heterocyclic scaffolds from readily available substrates18,23
herein, we report the first one-pot synthesis of benzimidazoles
and benzothiazoles from aromatic terminal olefins.
Based on the previous literature reports on alkene activation for
its further functionalisation,24 we initiated our study with styrene
1
a and o-Phenylenediamine 2a in the presence of Pd(OAc)
2
(5
Table 2. Scope of Styrenes and o-Phenylenediaminea
mol%), in AcOH under oxygen atmosphere. To our delight the
desired product 3a was isolated with 42% yield in 12 h at 70 C
o
H
o
Pd(OAc)2 (5 mol%),
N
(Table 1, entry 2). Increase of temperature to 80 C furnished 3a
H2N
H2N
R2
R
o
AcOH, 90 oC,
O2 ballon, 12 h
R
N
in 58% and to 90 C offered 3a in 71% yield (entries 3 & 4).
Additional increase in temperature did not improve the yield of
the products (entry 5). Moreover, increase in catalyst loading did
not enhance the yield of 3a (entry 6). Next, we have screened
various solvents such as DMSO, DMF, 1,4-dioxane, acetonitrile
and mixture of solvent like DMSO:AcOH (1:3) for further
improvement in yield. The results show that among the tested
solvents, AcOH is effective for this reaction (entries 7-11).
Conducting the reaction under open air and inert conditions
decreased the yield of 3a to 26% and 10%. In the absence of
catalyst, 3a formation was not observed (Table 1, entries 12-14).
With the optimized conditions (entry 4 in Table 1) in hand, we
next evaluated the generality of the method (Table 2).
1
R2
3
2
N
H
N
H
N
H
N
MeO
N
H
N
N
N
3
a, 71%
3b, 73%
3c, 53%
3d, 72%
N
R
H
H
N
N
N
R
COPh
R
R
R
N
H
N
H
N
N
R = Me, R = F, (3i, 57%)
R = Me, R = Cl, (3j, 51%)
R = OMe, R = Cl (3k, 54%)
R = H, (3l, 24%)
R = 4-Me, (3m, 27%)
R = 4-F, (3n, 21%)
R = F, (3e, 47%)
R = Br, (3f, 44%)
R = F, (3g, 49%)
R = Cl, (3h, 50%)
H
N
H
N
Cl
Cl
R
N
N
O N
2
3
q, 40%
R = Me, (3o, 57%)
R = F, (3p, 55%)
Table 1. Optimization of the Reaction Conditionsa
a
Reaction conditions: 0.25 mmol of 1a and 0.33 mmol of 2a in the presence of catalyst and in solvent (1 mL) at
N
9
0 °C for 12 h in oxygen atmosphere.
NH2
conditions
N
H
To further expand the scope of the reaction, we tested the
reactivity of 2-amino thiophenol (4) with styrene (1a) under
standard reaction conditions (table 3). To our delight 2-
phenylbenzo[d]thiazole (5a) was obtained with 60% yield.
Furthermore, both electron-rich and electron-poor styrenes (Table
NH2
a
1a
2
3a
Yieldb
(%)
Sr.
No.
Catalyst
(mol %)
Solvent
Temp
( C)
Time
(h)
o
3
5
) reacted well with 4 and afforded the products 5b, 5c, 5d, 5e &
f in good yields (30-66%). To further expand the scope of the
1
2
3
4
5
Pd(OAc)
Pd(OAc)
Pd(OAc)
2
2
2
(5)
(5)
(5)
(5)
(5)
AcOH
AcOH
AcOH
AcOH
AcOH
rt
12
12
12
12
12
n.r
42
58
71
68
70
80
90
100
above reaction, we have tested the reactivity of 2-aminophenol
with styrene 1a under standard conditions. Unfortunately, no
desired product was obtained (no reaction between 2-
aminophenol and styrene), starting materials were isolated.
Pd(OAc)
2
Pd(OAc)
2
6
7
Pd(OAc)
Pd(OAc)
2
(10)
(5)
AcOH
DMSO
100
90
12
12
70
16
2
2
Table 3. Scope of Styrenes and 2-Aminothiophenol
8
Pd(OAc)
(5)
DMF
90
12
trace
9
Pd(OAc)
Pd(OAc)
Pd(OAc)
2
2
2
(5)
(5)
(5)
Dioxane
90
90
90
12
12
12
n.r.
n.r.
66
H2N
Pd(OAc)2 (5 mol%)
S
N
1
1
0
1
3
CH CN
HS
AcOH, 12 h
R
DMSO:
AcOH
R
1
4
0 oC, O2
5
9
(
1:3)
1
1
1
2c
3d
4
Pd(OAc)
Pd(OAc)
--
2
2
(5)
(5)
AcOH
AcOH
AcOH
90
90
90
12
12
12
26
S
N
S
N
S
N
S
N
MeO
Br
10
n.r.
a
5a, 60%
5b, 65%
5c, 66%
5d, 35%
Reaction conditions : 0.25 mmol of 1a and 0.33 mmol of 2a in the presence of
MeO
MeO
catalyst and in solvent (1mL) at 90 °C for 12 h in oxygen atmosphere. b Isolated
yields, c open air condition, d inert condition.
S
N
S
N
Cl
We first examined the reactions of 2-amino anilines with
different styrenes under optimized reaction conditions. Simple,
methyl and methoxy styrenes produced corresponding
benzimidazoles 3a (71%), 3b (73%) & 3c (53%) in good yields.
Moreover, to enhance the substrate scope of styrenes, we have
5e, 30%
5f, 63%
reacted 1-vinyl-1H- imidazole (6) in place of styrenes with o-
a
Reaction conditions: 0.25 mmol of 1a and 0.33 mmol of 2a in the presence of catalyst and in solvent (2 mL) at
phenylenediamine (2) under standard conditions. Unfortunately,
9
0 °C for 12 h in oxygen atmosphere.
expected product (2-(1H-imidazol-1-yl)-1H-benzo[d]imidazole)

was not obtained. However, we have isolated 2-methyl-1H-
benzo[d]imidazole 7 via selective cleavage of the C–N bond of
vinyl-1H- imidazole (Table 4). o-Phenylenediamines with
different substituents successfully produced corresponding 2-
methyl-1H-benzo[d]imidazoles. Halogen substitutions like 4-
flouro, 4-chloro & 4-bromo o-phenylenediamines furnished
products 7b (63%), 7c (68%) and 7d (65%) in good yields. Also,
nitro & benzoyl substituted o-phenylenediamines reacted well
with 6 and produced 7e (61%), 7f (49%) with moderate yields.
Table 4. Scope of Vinylimidazole and o-Phenylenediamine
H2N
Pd(OAc)2 (5 mol%)
AcOH, 12h
N
N
N
Me
Me
H2N
N
H
0 oC, O2
9
6
2
7
N
F
N
Cl
N
Br
Me
N
Me
Me
N
H
N
H
N
H
N
H
(
7a, 77%)
(7b, 63%)
(7c, 68%)
(7d, 65%)
Scheme 3. Control Experiments
O
O2N
N
N
Ph
Me
Me
N
H
N
H
NH2
NH2
Ar
(
7f, 49%)
(
7e, 61%)
O
N
Pd(OAc)2
Ar
a
Reaction conditions: 0.25 mmol of 1a and 0.33 mmol of 2a in the presence of
Ar
ref 26
NH2
catalyst and in solvent (1 mL) at 90 °C for 12 h in oxygen atmosphere.
A
H O
2
Encouraged by these results, we became curious to test the fate
of allylbenzene, as our next substrate with o-phenylenediamine.
Interestingly, 2-aryl benzimidazole 3c was isolated with 61%
yield via C(sp3)-C(sp2) bond cleavage(Scheme 2).
H
N
H
N
Ar
N
Ar
Ar
H
N
H
N
H
N
H
H O
O2
O
2
3a
B
standard
conditions
H
N
C
NH2
NH2
OMe
N
MeO
8
2a
3c
Scheme 4. Proposed Mechanism
Scheme 2. Reactivity of Allylbenzene with o-Phenylenediamine
To gain a deep insight into the reaction mechanism, control
experiments were conducted (Scheme 3). When benzaldehyde (9)
was reacted with o-phenylenediamine under standard condition,
In summary, we have developed a palladium catalysed facile one
pot synthetic method for the synthesis of benzimidazoles and
benzothiazoles from readily available styrenes/vinyl imidazoles
and 2-amino/2-mercaptosubstituted anilines. This method
involves sequential C=C/C‒N bond cleavage followed by
C−N/C−S bond formation. Molecular oxygen used as sole
oxidant. Easy handling and smooth reaction conditions are the
salient features of this method.
3
a was observed with 32% yield and 2-aryl-1-arylmethyl-1H-1,3-
benzimidazole (10) formed as by-product with 22% yield.
However, we did not observe product 10 during reaction of
styrene (1a) with o-phenylenediamine under standard condition,
which ruled out the formation of benzaldehyde (9) as
intermediate. Under standard conditions Phenyl acetaldehyde
(11) afforded mixture of 3a & 12. Acetophenone (13) and 1-
phenylethane-1,2-diol (14) were independently employed to
standard conditions. Acetophenone (13) smoothly produced the
corresponding product 3a in 72% yield, whereas compound 14
was found to be unreactive (Scheme 3d). Moreover,
phenylglyoxal (15) produced 3a in 8% yield.
Acknowledgments
This work was supported by DBT (Grant GAP0556), New
Delhi. We are thankful to the NMR and Mass divisions of CSIR-
IICT for providing the analytical facilities. O.R, P.R thanks CSIR
and A. S. thank UGC for the Ph.D. fellowships. N.S. thanks DBT
for project fellowship. We thank Director CSIR-IICT for the
support (IICT/Pubs./2019/369).
2
6
Based on the control experiments and a previous report , we
propose a possible mechanism as shown in Scheme 4. Initially,
styrene (1a) undergoes oxidation in presence of catalytic amount
2
6
of palladium to give acetophenone . Subsequently, o-
phenylenediamine reacts with acetophenone to deliver A.
Intermediate A then cyclizes to give dihydro benzimidazole B.
Oxidation of intermediate B gives oxo derivative C. Subsequent
aromatization process will leads to the final product 3a with the
loss of formaldehyde.
References and notes
1.
(a) Zablotskaya, A.; Segal, I.; Geronikaki, A.; Eremkina, T.; Belyakov,
S.; Petrova, M.; Shestakova, I.; Zvejniecea, L.; Nikolajeva, V. Eur. J.
Med. Chem. 2013, 70, 846; (b) Cai, J.; Sun, M.; Wu, X.; Chen, J.;
Wang, P.; Zong, X.; Ji, M. Eur. J. Med. Chem. 2013, 63, 702; (c)
Nemeth-Konda, L.; Fuleky, G.; Morovjan, G.; Csokan, P.;
Ph
Ph
O
N
Pd(OAc)2 (5 mol%)
2
a
a
a)
3a (32%)
Ph
H
AcOH, 90 o
C
N
(22%)
10
9
H
N
Ph
b) Ph
standard conditions
2
3a

4
Tetrahedron
Chemosphere. 2002, 48, 545; (d) Prchal, L.; Podlipna, R.; Lamka, J.;
Chem. Int. Ed. 2014, 53, 13808; (h) Nguyen, T. B.; Ermolenko, L.; Al-
Mourabit, A. Synthesis 2015, 47, 1741; (i) Nguyen, T. B.; Pasturaud,
K.; Ermolenko, L.; Al-Mourabit, A. Org. Lett. 2015, 17, 2562; (j)
Nguyen, L. A.; Ngo, Q. A.; Retailleau, P.; Nguyen, T. B. Green Chem.
2017, 19, 4289.
Dedkova, T.; Skalova, L.; Vokral, I.; Lecova, L.; Vanek, T.; Szotakova,
B.; Environ. Sci. Pollut. Res. 2016, 23, 13015; (e) Zou, R.; Ayres, K. R.;
Drach, J. C.; Townsend, L. B. J. Med. Chem. 1996, 39, 3477. (f) Huang,
S.-T.; Hsei, I.-J.; Chen, C.; Bioorg. Med. Chem. 2006, 14, 6106; (g)
Osmaniye, D.; Levent, S.; Karaduman, A. B.; Ilgın, S.; Ozkay, Y.;
Kaplancikli, Z. A. Molecules, 2018, 23, 1054. (h) Bhrigu, B.; Siddiqui,
N.; Pathak D.; Alam, M. S.; Ali, R.; Azad, B. Acta Pol Pharm. 2012,
8.
9.
Daw, P.; Ben-David, Y.; Milstein, D. ACS Catal. 2017, 7, 7456.
Hikawa, H.; Ichinose, R.; Kikkawa, S.; Azumaya, I. Asian J. Org.
Chem. 2018, 7, 416.
6
9, 53.
10. Lai, Y. -L.; Ye, J. -S.; Huang, J. -M. Chem. Eur. J. 2016, 22, 5425.
11. Das, K.; Mondal, A.; Srimani, D. J. Org. Chem. 2018, 83, 9553.
12. Sharma, R.; Abdullaha, M.; Bharate, S. B. Asian J. Org. Chem. 2017, 6,
1370.
2
.
(a) Yadav, G.; Ganguly, S. Eur. J. Med. Chem. 2015, 97, 419; (b)
Bansal, Y.; Silakari, O.; Bioorg. Med. Chem. 2012, 20, 6208; (c) Min,
J.; Won, J.; Kang, Y. S.; Nagase, S. J. Photochem. Photobiol. A: Chem.
2
5
011, 219, 148; (d) Asensio, J. A.; Gomez-Romero, P. Fuel Cells. 2005,
, 336; (e) White, A. W.; Almassy, R.; Calvert, A. H.; Curtin, N. J.;
13. Zhang, R.; Qin, Y.; Zhang, L.; Luo S. Org. Lett. 2017, 19, 5629.
14. Naresh, G.; Kant, R.; Narender, T. J. Org. Chem. 2014, 79, 3821.
15. (a) Bougrin, K.; Soufiaoui, M. Tetrahedron Lett. 1995, 36, 3683. (b) Li,
Z.; Dong, J.; Chen, X.; Li, Q.; Zhou, Y.; Yin, S. -F. J. Org. Chem. 2015,
80, 9392.
16. (a) Kamila, S.; Koh, B.; Biehl, E. R. J. Heterocycl. chem. 2006, 43,
1609; (b) Kano, S.; Yuasa, Y.; Ono, T.; Shibuya, S. Heterocycles. 1979,
10.
Griffin, R. J.; Hostomsky, Z.; Golding, B. T. J. Med. Chem. 2000, 43,
084; (f) Battershill, A. J.; Scott, L. J. Drugs. 2006, 66, 51; (g) Gill, R.
K.; Rawaland Bariwal, R. K. J. Arch. Pharm. Chem. Life Sci. 2015, 348,
55; (h) Hartley, D.; Kidd, H.; The Agrochemical Handbook; Royal
4
1
Society of Chemistry: Nottingham, 1983; (i) Baker, D. R.; Basarab, G.
S.; Fenyes, J. G.; Synthesis and Chemistry of Agrochemicals IV;
American Chemical Society: Washington D. C. 1995. (j) Zhou, Y.;
Zhou, Z.; Li, Y.; Yang, W. Catal Commun. 2015, 64, 96.
17. (a) Mayo, M. S.; Yu, X.; Zhou, X.; Feng, X.; Yamamoto, Y.; Bao, M.
Org. Lett. 2014, 16, 764; (b) Wang, Z. X.; Qin, H. L. J.
Heterocycl.chem. 2005, 42, 1001.
3
4
.
.
(a) Gadekar, L. S.; Arbad, B. R.; Lande, M. K. Chin.Chem. Lett. 2010,
2
3
2
1, 1053; (b) Zhang, C.; Zhang, L.; Jiao, N. Green Chem. 2012, 14,
273; (c) Mukhopadhyay, C.; Tapaswi, P. K. Catal. Commun. 2008, 9,
392; (d) Tumelty, D.; Cao, K.; Holmes, C. P. Org. Lett. 2001, 3, 83;
18. Ravi, O.; Shaikh, A.; Upare, A.; Singarapu, K. K.; Bathula, S. R. J.
Org. Chem. 2017, 82, 4422.
19. Corey, E.J.; Cheng, X. -M. The Logic of Chemical Synthesis, John
Wiley, New York, 1989.
20. Evans. P. A.; Tsuji, J. Modern Rhodium-Catalyzed Organic Reactions
Wiley-VCH. 2005, 93.
(e) Wu, Z.; Rea, P.; Wickham, G. Tetrahedron Lett. 2000, 41, 9871; f)
Bahrami, K.; Khodaei, M. M.; Nejati, A. Green Chem. 2010, 12, 1237.
(a) Dubois, N.; Glynn, D.; McInally, T.; Rhodes, B.; Woodward, S.;
Irvine, D. J.; Dodds, C. Tetrahedron. 2013, 69, 9890; (b) Pinder, J. L.;
Davis, R. E.; Charrier, J.-D. Tetrahedron Lett. 2014, 55, 4853; (c)
Tandon, V. K.; Kumar, M. Tetrahedron Lett. 2004, 45, 4185; (d)
Bommegowda, Y. K.; Lingaraju, G. S.; Thamas, S.; Kumar, K. S. V.;
Kumara, C. S. P.; Rangappa, K. S.; Sadashiva, M. P. Tetrahedron Lett.
21. Takacs, J. M.; Jiang, X. -T. Curr. Org. Chem. 2003, 7, 369.
22. (a) Hoveyda, A.H.; Zhugralin, A. R. Nature. 2017, 450, 243; (b)
Connon, S.J.; Blechert, S. Angew. Chem. Int. Ed. 2003, 42, 1900.
23. (a) Ramaraju, A.; Chouhan, N. K.; Ravi, O.; Sridhar, B.; Bathula, S. R.
Eur. J. Org. Chem. 2018, 2963; (b) Ravi, O.; Ramaraju, A.; Sridhar, B.;
Bathula, S. R. Adv. Synth. Catal. 2018, 360, 3009; (c) Upare, A.;
Sathyanarayana, P.; Kore, R.; Sharma, K.; Bathula, S. R. Tetrahedron
Lett. 2018, 59, 2430; (d) Sathyanarayana, P.; Upare, A.; Ravi, O.;
Muktapuram P. R.; Bathula, S. R. RSC Adv. 2016, 6, 22749; (e)
Sathyanarayana, P.; Ravi, O.; Muktapuram, P. R.; Bathula, S. R. Org.
Biomol. Chem. 2015, 13, 9681; (f) Viswanadham K. D. R.;
Muktapuram, P. R.; Sathyanarayana, P.; Ravi, O.; Kant, R.; Bathula, S.
R. Chem. Commun. 2014, 50, 13517; (g) Bathula, S. R.; Muktapuram,
P. R.; Viswanadham K. D. R.; Sathyanarayana, P.; Reddy, M. S. Eur. J.
Org. Chem. 2013, 2013, 4552.
24. (a) Cornell, C. N.; Sigman, M. S. Inorg. Chem. 2007, 46, 1903; (b) Wu,
W.; Jiang, H. Acc Chem Res. 2012, 45, 1736; (c) Wang, A.; Jiang, H. J.
Org. Chem. 2010, 75, 2321; (d) (m) Dhakshinamoorthy, A.; Alvaro, M.;
Garcia, H. ACS Catal. 2011, 1, 836; (e) Xing, D.; Guan, B.; Cai, G.;
Fang, Z.; Yang, L.; Shi, Z. Org. Lett. 2006, 8, 693; (f) Wang, T., Jiao,
N. J. Am. Chem. Soc. 2013, 135, 11692.
25. In case of styrenes with deactivating substituents such as fluoro, bromo
and nitro, reaction requires 0.75 mmol of corresponding styrene for
completion.
2
3
013, 54, 2693. (e) Nguyen, T. B.; Retailleau, P. Org. Lett. 2017, 19,
887.
5
6
7
.
.
.
(a) Shiraishi, Y.; Sugano, Y.; Tanaka, S.; Hirai, T. Angew. Chem. Int.
Ed. 2010, 49, 1656; (b) Xu, C.; Xiao, Z. Q.; Li, H. M.; Han, X.; Wang,
Z. Q.; Fu, W. J.; Ji, B. M.; Hao, X. Q.; Song, M. P. Euro. J. Org. Chem.
2
2
S. P.; Saidi, O.; Williams, J. M. Org. Lett. 2009, 11, 2039; (e) Shi, X.;
Guo, J.; Liu, J.; Ye, M.; Xu, Q. Chem. Euro. J. 2015, 21, 9988; (f) Xu,
Z.; Wang, D. -S.; Yu, X.; Yang, Y.; Wang, D. Adv. Synth. Catal. 2017,
3
3
2
Wang, D. Org. Chem. Front. 2019, 6, 3420.
(a) Nguyen, T. B.; Ermolenko, L.; Al-Mourabit, A. Green Chem. 2013,
1
Mourabit, A. Org. Lett. 2012, 14, 5948; (c) Yu, J.; Xia, Y.; Lu, M.
Synth Commun. 2014, 44, 3019; (d) Naresh, G.; Kant, R.; Narender, T.
J. Org. Chem. 2014, 79, 3821; (e) Dong, C. –P.; Higashiura, Y.; Marui,
K.; Kumazawa, S.; Nomoto, A.; Ueshima, M.; Ogawa, A. ACS Omega,
015, 2015, 7427; (c) Sun, Z.; Bottari, G.; Barta, K. Green Chem.
015, 17, 5172; (d) Blacker, A. J.; Farah, M. M.; Hall, M. I.; Marsden,
59, 3332; (g) Wang, D.; Albero, J.; García, H.; Li, Z. J. Catal. 2017,
49, 156; (h) Xu, Z.; Yu, X.; Sang, X. and Wang, D. Green Chem. 2018,
0, 2571; (i) Qiu, Y.; Zhang, Y.; Jin, L.; Pan, L.; Du, G.; Yeb, D.;
5, 2713; (b) Nguyen, T. B.; Ermolenko, L.; Dean, W. A.; Al-
26. Mitsudome, T.; Umetani, T.; Nosaka, N.; Mori, K.; Mizugaki, T.;
Ebitani, K.; Kaneda, K. Angew. Chem. Int. Ed. 2006, 45, 481.
2
016, 1, 799; (f) Liu, J.; Wang, C.; Ma, X.; Shi, X.; Wang, X.; Li, H.;
Xu, Q. Catal Lett. 2016, 146, 2139; (g) Reddy, P. L.; Arundhathi, R.;
Tripathi, M.; Chauhan, P.; Yan, N.; Rawat, Diwan S. ChemistrySelect,
Supplementary Material
2
017, 2, 3889; (h) Su, C.; Tandiana, R.; Balapanuru, J.; Tang, W.;
Pareek, K.; Nai, C. T.; Hayashi,T.; Loh, K. P. J. Am. Chem. Soc. 2015,
37, 685.
(a) Nguyen, T. B.; Ermolenko, L.; Al-Mourabit, A. J. Am. Chem. Soc.
1
Supplementary material that may be helpful in the review
process should be prepared and provided as a separate electronic
file. That file can then be transformed into PDF format and
submitted along with the manuscript and graphic files to the
appropriate editorial office.
2
2
012, 135, 118; (b) Xu, Z.; Yu, X.; Sang, X. and Wang, D. Green Chem.
018, 20, 2571; (c) Qiu, Y.; Zhang, Y.; Jin, L.; Pan, L.; Du, G.; Yeb, D.;
Wang, D. Org. Chem. Front. 2019, 6, 3420; (d) Nguyen, T. B.;
Ermolenko, L.; Al-Mourabit, A. Org. Lett. 2013, 15, 4218; (e) Nguyen,
T. B.; Bescont, J. L.; Ermolenko, L.; Al-Mourabit, A. Org. Lett. 2013,
1
5, 6218; (f) Nguyen, T. B.;Bescont, J. L.; Ermolenko, L.; Corbin, M.;
Al-Mourabit, A. Org. Chem. Front.2014, 1, 1157; (g) Dr. Nguyen, T.
B.; Dr. Ermolenko, L.; Dr. Retailleau, P.; Dr. Al-Mourabit, A. Angew.

NH2
XH
N
N
X
N
R1
Pd(OAc)2 (5 mol%),
Pd(OAc)2 (5 mol%),
Me
R1
Ar
o
o
AcOH, 90 C, O
AcOH, 90 C, O2
2
R1
N
N
X = S, NH
R2
X = S, NH

6
Tetrahedron

Practical synthetic method for Benzimidazoles
and benzthiazoles has been developed.
Easy handling & smooth reaction conditions are
the salient features of this method.



Molecular oxygen used as sole oxidant.
Reaction involves Palladium Catalysed
Oxidative C=C and C‒N bond Cleavage.