Microwave assisted one pot synthesis of 2-ethylamino benzimidazole, benzoxazole and benzothiazole derivatives

Article abstract of DOI:10.1080/00397911.2019.1599952

A rapid and efficient one-pot method for the synthesis of 2-ethylamino benzimidazole, benzoxazole, and benzothiazole derivatives has been described. The reaction of o-phenylenediamines or o-aminophenols or 2-mercaptoanilines with EDC.HCl under microwave irradiation afforded the corresponding 2-ethylamino benzimidazole, benzoxazole and benzothiazole derivatives in excellent yields.

Full text of DOI:10.1080/00397911.2019.1599952

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: https://www.tandfonline.com/loi/lsyc20
Microwave assisted one pot synthesis of 2-
ethylamino benzimidazole, benzoxazole and
benzothiazole derivatives
Thirupathi Rapolu, Pavan Kumar K. V. P., Korupolu Raghu Babu, Satheesh
Kumar Dende, Rajashekar Reddy Nimmareddy & Leleti Krishnakanth Reddy
To cite this article: Thirupathi Rapolu, Pavan Kumar K. V. P., Korupolu Raghu Babu, Satheesh
Kumar Dende, Rajashekar Reddy Nimmareddy & Leleti Krishnakanth Reddy (2019): Microwave
assisted one pot synthesis of 2-ethylamino benzimidazole, benzoxazole and benzothiazole
derivatives, Synthetic Communications, DOI: 10.1080/00397911.2019.1599952
To link to this article: https://doi.org/10.1080/00397911.2019.1599952
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https://doi.org/10.1080/00397911.2019.1599952
Microwave assisted one pot synthesis of 2-ethylamino
benzimidazole, benzoxazole and benzothiazole derivatives
Thirupathi Rapolua,b, Pavan Kumar K. V. P.a, Korupolu Raghu Babub, Satheesh
Kumar Dendea,b, Rajashekar Reddy Nimmareddya,b, and Leleti
Krishnakanth Reddya
b
aMedicinal Chemistry Division, GVK Biosciences Private Limited, Hyderabad, India; Department of
Engineering Chemistry, Andhra University College of Engineering (A), Visakhapatnam, India
ABSTRACT
ARTICLE HISTORY
Received 1 February 2019
A rapid and efficient one-pot method for the synthesis of 2-ethyla-
mino benzimidazole, benzoxazole, and benzothiazole derivatives has
been described. The reaction of o-phenylenediamines or o-amino-
phenols or 2-mercaptoanilines with EDC.HCl under microwave irradi-
ation afforded the corresponding 2-ethylamino benzimidazole,
benzoxazole and benzothiazole derivatives in excellent yields.
KEYWORDS
Benzazoles; 2-ethylamino
benzazoles; micro-
wave synthesis
GRAPHICAL ABSTRACT
EDC.HCl, ipropanol
NH2
N
X
R
R
NH
XH
80 °C, MW, 15 min
X= NH, O, S
Introduction
Benzazoles represent an important class of fused bicyclic systems consisting of benzene
and imidazole or oxazole or thiazole rings. Substituted benzimidazole,[1] benzoxazole,[2]
and benzothiazole[3] derivatives were found to have great synthetic value due to their
biological activity in pharmacological screening. Most of the reported methods for the
synthesis of 2-alkylamino benzimidazoles involve multi-steps with lower yields and lon-
ger reaction time.[4,5] Biological activity and pharmacological importance of these com-
pounds have prompted us to develop a synthetic method which is cost effective with
shorter reaction time. Recently, the synthesis of 2-ethylamino benzazole derivatives has
been reported.[6] However, these methods involve longer reaction time and lower yield.
In this respect, microwave-assisted organic synthesis has been found to be most effective
because of high reaction rates with improved yields.[7] In continuation of our endeavor
to develop simple protocols using the microwave,[8] we wish to describe the results of
CONTACT Leleti Krishnakanth Reddy
krishna.leleti@gvkbio.com
Medicinal Chemistry Division, GVK Biosciences
Private Limited, 28A, IDA Nacharam, Hyderabad, 500076, India.
Supplemental data for this article is available online at on the publisher’s website.
ß 2019 Taylor & Francis Group, LLC

2
T. RAPOLU ET AL.
EDC.HCl, ipropanol
80 °C, MW, 15 min
NH2
XH
N
X
R
R
NH
X= NH, O, S
Scheme 1. Synthesis of 2-ethylamino benzazole derivatives.
Table 1. Optimization of the reaction conditions for the synthesis of 2-ethylamino benzimidazole
from o-phenylenediamine and EDC.HCl under conventional and microwave heating in different sol-
vents.
NH2
EDC.HCl
N
NH
N
H
NH2
1
1a
Conventional heating
Microwave Heating
S.No.
Solvents
Temperature (oC)
Time (hrs)
Yield (%)
Temperature (oC)
Time (min)
Yield (%)
1
2
3
4
5
6
Methanol
THF
Ethanol
2-Propanol
Acetonitrile
DMF
65
67
80
83
83
24
24
24
24
24
24
38
15
42
45
25
30
80
80
80
80
80
80
15
15
15
15
15
15
60
45
63
90
55
56
150
microwave supported synthesis of 2-ethylamino benzimidazole, benzoxazole, and benzo-
thiazole derivatives (Scheme 1).
Results and discussion
To check the feasibility of the reaction, a mixture of o-phenylenediamine (1) and
EDC.HCl in methanol was heated at 65 ꢀC for 24 h. After workup, the crude product
1
obtained was purified by column chromatography over silica gel. HNMR and HRMS
spectra of the product indicated the formation of compound 1a (Table 1). To optimize
the conventional method, different solvents were screened. The optimal condition for
i
the better conversion of starting material has been found in propanol at 83 ꢀC with
24 h reaction time and a 45% yield of the product. The experimental results showed the
presence of starting material by TLC even after 24 h, resulting in lower yield. To com-
pare the results of the conventional method, a model reaction has been performed with
o-phenylenediamine and EDC.HCl under microwave heating using different solvents
and tabulated the results in Table 1 and found that better yields (90%) were obtained in
ipropanol at 80 ꢀC with 15 min reaction time which is much lower when compared to
conventional method. We also checked the effect of solvent on the product yields and
came up with an observation that protic solvents afforded slightly better yields com-
pared to aprotic solvents.
After observing positive results using the microwave, different N-substituted and aryl
substituted o-phenylenediamines were tried. In all the cases, reactions proceeded to

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SYNTHETIC COMMUNICATIONSV
3
Table 2. Synthesis of 2-ethylamino benzazole derivatives under microwave irradiation.a
EDC.HCl, ipropanol
NH2
N
X
R
R
NH
XH
80 °C, MW, 15 min
X= NH, O, S
Entry Starting material
Productb
Yield (%)c
NH2
R
N
N
R = H (1a)(6a)
90
89
85
NH
R = Methyl (1b)(9a)
1
2
3
N
H
R = Cyclopropyl (1c)
R
1a-c
1
R' = 5-tert Butyl (2a)
R' = 5-Cyano (2b)
R' = 5-Nitro (2c)
94
75
79
81
80
R'
X
R'
X
NH2
N
NH
NH2
N
H
R' = 5-Methyl (2d)(9b)
2
2a-e
R' = 5-Trifluoromethyl (2e)
N
X = 5-Fluoro (3a)
X = 5-Chloro (3b)
X = 5-Bromo (3c)
X = 5,6-Dichloro (3d)
NH2
NH2
80
84
88
82
NH
N
H
3
3a-d
N
NH2
NH2
NH
4
5
6
88
95
75
N
H
4
4a
O
NH2
NH2
O
O
N
F
F
F
F
NH
O
N
H
5a
5
N
NH2
NH2
N
N
NH
NH
N
H
6
6a
NH2
OH
N
O
7
90
7a6b
7
(continued)
completion with good yields ranging from 75 to 95% showing the applicability of this
method over a wide range of substrates. Further to widen the scope of the method, o-
aminophenols and 2-mercaptoanilines were treated with EDC.HCl under microwave
irradiation to afford the corresponding 2-ethylamino benzoxazole and benzothiazole

4
T. RAPOLU ET AL.
R' = 5-tert Butyl (8a)
R' = 5-Cyano (8b)
R'
94
75
79
81
80
NH2
OH
R'
X
N
O
NH
R' = 5-Nitro (8c)(9c)
R' = 5-Methyl (8d)(9d)
R' = 5-methoxy (8e)
8
9
8
8a-e
X
N
O
NH2
OH
NH
X = 5-Chloro (9a)(9e)
80
88
9
9a
NH2
N
NH
O
10
11
OH
10
10 a
NH2
OH
N
O
R
R' = 4-Methyl (11a)
R' = 7-Methyl (11b)
95
90
R
NH
11a-b
11
12
NH2
N
S
NH
R = H (12a)(6c)
90
12
13
SH
12a
X
X
N
NH2
SH
R' = 5-Bromo (13a)
R' = 5-Chloro (13b)
R' = 6-Bromo (13c)
R' = 6-Chloro (13d)(9f)
94
75
79
81
NH
S
13a-d
13
a: All the reactions were carried out using starting material (1.0 mmol), EDC.HCl (1.1 mmol) in
iso-propanol at 80 °C for 15 min under microwave irradiation.
b: All the products were characterized by 1H, 13C NMR and mass spectroscopy.
c: Isolated yields after column chromatography.
derivatives, respectively in excellent yields. It was observed that the substitution on aro-
matic ring plays an important role in the product yields. The withdrawing groups on
the aromatic ring gave lower yields compared to the donating groups. This may be due
to the electronic effects of withdrawing and donating groups on the basicity of amines
(Table 2).
The plausible mechanism for the formation of 2-ethylamino benzazole derivatives can
be explained by the nucleophilic addition of amines on electrophilic carbon of diimide
leading to the formation of dihydro benzazole intermediate followed by the elimination
of amine E. The predominant elimination of amine E over the ethyl amine could pos-
sibly be due to the formation of hydrogen bonding (Figure 1).
In conclusion, we have demonstrated one-pot synthesis of 2-ethylamino benzazole
derivatives by the reaction of o-phenylenediamines or o-aminophenols or 2-mercaptoa-
nilines and EDC.HCl under microwave irradiation. The attractive features of the

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SYNTHETIC COMMUNICATIONSV
5
N
N C N
NH2
XH
N
N
H
R
N
H
N
R
R
N
NH
NH
X
NH
N
X
N
H
XH
H2N
N
E
H
R
d
N
N
N
H
X
NH
Figure 1. Plausible mechanism for the formation of 2-ethylamino benzazole derivatives.
method are single-step synthesis with improved yields and shorter reaction time which
makes it a useful method for the synthesis of 2-ethylamino benzazole derivatives.
Representative procedure
A mixture of o-phenylenediamine (1) (1.0 mmol) and EDC.HCl (1.1 mmol) in 2-pro-
panol (10 mL) was irradiated in microwave apparatus at 200 W (80 ꢀC) for 15 min.
Reaction was monitored by TLC (eluent CH2Cl2/MeOH 95:5). After completion, the
reaction mixture was diluted with water (20 mL) and extracted with EtOAc (2 ꢁ 25 mL).
,
The combined organic layers were washed with brine, dried over anhydrous Na2SO4
and concentrated under reduced pressure and the obtained crude product was purified
by flash column chromatography using silica gel (100–200 mesh) with 1–5% MeOH/
CH2Cl2 as eluent. The fractions containing product were collected and concentrated
under reduced pressure to afford N-ethyl-1H-benzo[d]imidazol-2-amine (1a, 90% yield)
as an off white solid. IR (KBr)tmax: 3403, 3053, 2966, 2869, 2721, 2659, 1916, 1873,
1760, 1640, 1599,1584, 1512, 1462, 1348, 1253, 1141, 1121, 1020, 917, 843, 746, 678,
1
579 cmꢂ1. Melting Range: 138–141 ꢀC, H NMR (400 MHz, DMSO-d6) d ¼ 10.60 (br s,
1H), 7.12–7.08 (m, 2H), 6.91–6.82 (m, 2H), 6.48 (br s, 1H), 3.33–3.27 (m, 2H), 1.17 (t,
J ¼ 7.1 Hz, 3H), 13C NMR (DMSO-d6, 100 MHz): d 155.4, 138.7, 118.8, 111.4, 40.1, 39.9,
39.7, 39.5, 39.2, 39.0, 38.8, 36.9, 15.1; HRMS (ESI) m/z calcd. for C9H11N3 ([M þ H]þ)
162.0953; found: 162.0108
Acknowledgments
The authors are thankful to GVK Biosciences Private Limited management for constant encour-
agement and providing facilities for accomplishing this research. Help from the analytical depart-
ment for all spectroscopic analysis is highly appreciated. We are grateful to Dr. Sudhir Kumar
Singh (President, Discovery and Development Services, GVK Biosciences) for his immense sup-
port and motivation. We are also thankful to AU, Visakhapatnam.
Supporting information
1
General experimental procedures, IR, H, 13C NMR and mass spectra. This material can be found
via the “Supplementary Content” section of this article’s webpage.

6
T. RAPOLU ET AL.
References
[1] (a) Salahuddin, M. S.; Mazumder, A. Benzimidazoles: A biologically active compounds.
Arab. J. Chem. 2017, 10, S157. DOI: 10.1016/j.arabjc.2012.07.017. (b) Reuter, S.; Jensen,
B.; Buttenschoen, K.; Kratzer, W.; Kern, P. Benzimidazoles in the Treatment of Alveolar
Echinococcosis: A Comparative Study and Review of the Literature. J. Antimicrob.
Chemother. 2000, 46, 451. DOI: 10.1093/jac/46.3.451.
[2] Boyd, G. V. Oxazoles and their Benzo Derivatives. In Comprehensive Heterocyclic
Chemistry. Katritzky, A. R., Rees, C. W., Eds.; Elsevier, 1984; Vol. 6, pp 177.
[3] Metzger, J. V. Thiazoles and their Benzo Derivatives. In Comprehensive Heterocyclic
chemistry. Katritzky, A. R.; Rees, C. W., Eds.; Elsevier, 1984; Vol. 6, pp. 235.
[4] (a) Zhu, J.; Wu, C.-F.; Li, X.; Wu, G.-S.; Xie, S.; Hu, Q.-N.; Deng, Z.; Zhu, M. X.; Luo,
H.-R.; Hong, X. Synthesis, Biological Evaluation and Molecular Modeling of Substituted
2-Aminobenzimidazoles
as
Novel
Inhibitors
of
Acetylcholinesterase
and
Butyrylcholinesterase. Bioorg. Med. Chem. 2013, 21, 4218. DOI: 10.1016/j.bmc.2013.05.001.
(b) Vlaar, T.; Cioc, R. C.; Mampuys, P.; Maes, B. U. W.; Orru, R. V. A.; Ruijter, E.
Sustainable Synthesis of Diverse Privileged Heterocycles by Palladium-Catalyzed Aerobic
Oxidative Isocyanide Insertion. Angew. Chem. Int. Ed. Engl. 2012, 51, 13058. DOI:
10.1002/anie.201207410. (c) Zhu, T.-H.; Wang, S.-Y.; Wang, G.-N.; Ji, S.-J. Cobalt-
Catalyzed Oxidative Isocyanide Insertion to Amine-Based Bisnucleophiles: Diverse
Synthesis of Substituted 2-Aminobenzimidazoles, 2-Aminobenzothiazoles, and 2-
Aminobenzoxazoles. Chemistry. 2013, 19, 5850. DOI: 10.1002/chem.201300239. (d) Zhu,
T.-H.; Xu, X.-P.; Cao, J.-J.; Wei, T.-Q.; Wang, S.-Y.; Ji, S.-J. Cobalt(II)-Catalyzed
Isocyanide Insertion Reaction with Amines under Ultrasonic Conditions: A Divergent
Synthesis of Ureas, Thioureas and Azaheterocycles. Adv. Synth. Catal. 2014, 356, 509.
DOI: 10.1002/adsc.201300745.(e) Yu, H.; Liu, Q.; Li, Y.; Ni, C. Copper-Catalyzed
Synthesis of 2-Aminobenzimidazoles from Carbonimidoyl Dichlorides and Amines.
Tetrahedron Lett. 2012, 53, 5253. DOI: 10.1016/j.tetlet.2012.07.072. (f) Chi, Y.; Zhang, W.-
X.; Xi, Z. Oxidant-Switchable Selective Synthesis of 2-Aminobenzimidazoles via C–H
Amination/Acetoxylation of Guanidines. Org. Lett. 2014, 16, 6274. DOI: 10.1021/
ol502815p.(g) Wang, F.; Cai, S.; Liao, Q.; Xi, C. A Protocol to 2-Aminobenzimidazoles via
Copper-Catalyzed Cascade Addition and Cyclization of o-Haloanilines and Carbodiimides.
J. Org. Chem. 2011, 76, 3174. DOI: 10.1021/jo200014v. (h) Li, F.; Xie, J.; Shan, H.; Sun,
C.; Chen, L. General and Efficient Method for Direct N-Monomethylation of Aromatic
Primary Amines with Methanol. RSC Adv. 2012, 2, 8645. DOI: 10.1039/c2ra21487c. (i) Da
Settimo, A.; Marini, A. M.; Bianucci, A. M.; Primofiore, G.; Da Settimo, F.; Boldrini, E.
Synthesis of 2-Methylaminobenzimidazole Derivatives Tested for Antiinflammatory
Activity. Farmaco. 1994, 49, 829.(j) Quast, H.; Philipp, G.; Ross, K.-H.; Doht, U. M. Stable
3-Imino-2,3-Dihydroindazol-1-yl Radicals. Eur. J. Org. Chem. 2011, 2011, 1891. DOI:
10.1002/ejoc.201001659.(k) Quast, H.; Ross, K.-H.; Philipp, G.; Hagedorn, M.; Hahn, H.;
Banert, K. Syntheses and 15 N NMR Spectra of Iminodiaziridines – Ring-Expansions of
1-Aryl-3-Iminodiaziridines to 1 H – and 3a H –Benzimidazoles, 2 H – Indazoles, and 5 H
– Dibenzo[ d, f ][1,3]Diazepines. Eur. J. Org. Chem. 2009, 2009, 3940. DOI: 10.1002/
ejoc.200900350.(l) Quast, H.; Ross, K.-H.; Philipp, G. Thermal Rearrangements of
(Arylimino)Diaziridines by Simultaneous Cascades of Pericyclic Reactions. Eur. J. Org.
Chem. 2010, 2010, 2212. DOI: 10.1002/ejoc.200901474.
[5] (a) Gu, Z.-S.; Chen, W.-X.; Shao, L.-X. N-Heterocyclic Carbene-Palladium(II)-1-
Methylimidazole Complex-Catalyzed Direct C–H Bond Arylation of (benz)imidazoles with
Aryl Chlorides. J. Org. Chem. 2014, 79, 5806. DOI: 10.1021/jo5010058.(b) Chen, J.; Xiong,
X.; Chen, Z.; Huang, J. Imidazolium Salt Catalyzed para-Selective Halogenation of
Electron-Rich Arenes. Synlett. 2015, 26, 2831. DOI: 10.1055/s-0035-1560376. (c) Mahesh,
D.; Sadhu, P.; Punniyamurthy, T. Copper(I)-Catalyzed Regioselective Amination of N-Aryl
Imines Using TMSN3 and TBHP: A Route to Substituted Benzimidazoles. J. Org. Chem.
2015, 80, 1644. DOI: 10.1021/jo502574u. (d) Mahesh, D.; Sadhu, P.; Punniyamurthy, T.

R
SYNTHETIC COMMUNICATIONSV
7
Copper(II)-Catalyzed Oxidative Cross-Coupling of Anilines, Primary Alkyl Amines, and
Sodium Azide Using TBHP: A Route to 2-Substituted Benzimidazoles. J. Org. Chem. 2016,
81, 3227. DOI: 10.1021/acs.joc.6b00186. (e) Hu, Z.; Zhao, T.; Wang, M.; Wu, J.; Yu, W.;
Chang, J. I2-Mediated Intramolecular C-H Amidation for the Synthesis of N-Substituted
Benzimidazoles. J. Org. Chem. 2017, 82, 3152DOI: 10.1021/acs.joc.7b00142. (f) Nguyen,
T. B.; Ermolenko, L.; Dean, W. A.; Ali, A.-M. Benzazoles from Aliphatic Amines and o-
Amino/Mercaptan/Hydroxyanilines: Elemental Sulfur as a Highly Efficient and Traceless
Oxidizing Agent. Org. Lett. 2012, 14, 5948. DOI: 10.1021/ol302856w. (g) Nguyen, T. B.;
Ermolenko, L.; Ali, A. M. Sodium Sulfide: A Sustainable Solution for Unbalanced Redox
Condensation Reaction between o-Nitroanilines and Alcohols Catalyzed by an Iron–Sulfur
System. Synthesis. 2015, 47, 1741. DOI: 10.1055/s-0034-1380134. (h) Nguyen, T. B.;
Bescont, J. L.; Ermolenko, L.; Ali, A.-M. Cobalt- and Iron-Catalyzed Redox Condensation
of o-Substituted Nitrobenzenes with Alkylamines: A Step- and Redox-Economical
Synthesis of Diazaheterocycles. Org. Lett. 2013, 15, 6218. DOI: 10.1021/ol403064z. (i)
Mayo, M. S.; Yu, X.; Zhou, X.; Feng, X.; Yamamoto, Y.; Bao, M. Convenient Synthesis of
Benzothiazoles and Benzimidazoles Through Brønsted Acid Catalyzed Cyclization of 2-
Amino Thiophenols/Anilines with b-Diketones. Org. Lett. 2014, 16, 764. DOI: 10.1021/
ꢀ
ol403475v. (j) Bastug, G.; Eviolitte, C.; Marko, I. E. Functionalized Orthoesters as
Powerful Building Blocks for the Efficient Preparation of Heteroaromatic bicycles. Org.
Lett. 2012, 14, 3502. DOI: 10.1021/ol301472a. (k) Hati, S.; Dutta, P. K.; Dutta, S.; Munshi,
P.; Sen, S. Accessing Benzimidazoles via a Ring Distortion Strategy: An Oxone Mediated
Tandem Reaction of 2-Aminobenzylamines. Org. Lett. 2016, 18, 3090. DOI: 10.1021/
acs.orglett.6b01217. (l) Caron, S.; Jones, B. P.; Wei, L. Preparation of Substituted
Benzimidazoles and Imidazopyridines Using 2,2,2-Trichloroethyl Imidates. Synthesis. 2012,
44, 3049. DOI: 10.1055/s-0032-1317019. (m) Bahrami, K.; Khodaei, M. M.; Naali, F. Mild
and Highly Efficient Method for the Synthesis of 2-Arylbenzimidazoles and 2-
Arylbenzothiazoles. J. Org. Chem. 2008, 73, 6835. DOI: 10.1021/jo8010232. (n) Kim, Y.;
Kumar, M. R.; Park, N.; Heo, Y.; Lee, S. Copper-Catalyzed, One-Pot, Three-Component
Synthesis of Benzimidazoles by Condensation and C–N Bond Formation. J. Org. Chem.
2011, 76, 9577. DOI: 10.1021/jo2019416. (o) Baars, H.; Beyer, A.; Kohlhepp, S. V.; Bolm,
C. Transition-metal-free synthesis of benzimidazoles mediated by KOH/DMSO. Org. Lett.
2014, 16, 536. DOI: 10.1021/ol403414v. (p) Alla, S. K.; Kumar, R. K.; Sadhu, P.;
Punniyamurthy, T. Iodobenzene Catalyzed C–H Amination of N-Substituted Amidines
Using m-Chloroperbenzoic Acid. Org. Lett. 2013, 15, 1334. DOI: 10.1021/ol400274f.
[6] (a) Caroti, P.; Ceccotti, C.; Da Settimo, F.; Primofiore, G.; Franzone, J. S.; Reboani, M. C.;
Cravanzola, C. Synthesis, Antilipidemic and Platelet Antiaggregatory Activity of 2-amino-
benzimidazole amide derivatives. Farmaco. 1989, 44, 227. ISSN: 0014-827X. (b) Wang, J.;
Hou, J.-T.; Wen, J.; Zhang, J.; Yu, X.-Q. Iron-Catalyzed Direct Amination of Azoles Using
Formamides or Amines as Nitrogen Sources in Air. Chem. Commun. (Camb.). 2011, 47,
3652. DOI: 10.1039/c0cc05811d. (c) Yu, M.; Wang, B.; Zhou, P.; Jia, X.; Yuan, Y. Copper-
Promoted Direct C-H Aminationof Benzothiazoles Using Formamides as Nitrogen
Sources: An Efficient Approach for Synthesis of 2-Aminothiazoles. ChemistrySelect. 2016,
1, 6217. references cited therein. DOI: 10.1002/slct.201601552.
[7] Kahveci, B.; Mentese, E. Microwave-Assisted Synthesis of Benzimidazoles and Their
Derivatives from 1994 to 2016-A Review. Curr. Microwave Chem. 2017, 4, 73. DOI:
10.2174/2213335603666160517154048.
[8] (a) Deb, P. K.; Sharma, S.; Borude, A.; Singh, R. P.; Kumar, D.; Reddy, L. K. An Efficient
One-Pot Microwave Assisted Synthesis of Dibenzoazepinones. Tetrahedron Lett. 2013, 54,
2916. DOI: 10.1016/j.tetlet.2013.03.065. (b) Rao, K. P.; Basak, A. K.; Deb, P. K.; Sharma,
S.; Reddy, L. K. Microwave Assisted Palladium-Catalyzed Synthesis of Phthalazinones and
Pyridopyridazinones. Tetrahedron Lett. 2013, 54, 3694. DOI: 10.1016/j.tetlet.2013.05.006.
(c) Rao, K. P.; Basak, A. K.; Raju, A.; Patil, V. S.; Reddy, L. K. Microwave Assisted
Efficient Aminocarbonylation of N-Tosylhydrazones with Molybdenum Hexacarbonyl and
Amines. Tetrahedron Lett. 2013, 54, 5510. DOI: 10.1016/j.tetlet.2013.07.149.

8
T. RAPOLU ET AL.
[9] (a) Castellanos, M. L.; Llinas, M.; Bruix, M.; De Mendoza, J.; Martin, M. R. Nucleophilic
substitution in quaternary salts of NN0-linked biazoles and related systems. J. Chem. Soc.,
Perkin Trans. 1 1985, 6, 1209. DOI: 10.1039/P19850001209. (b) Frachey, G.; Crestini, C.;
Bernini, R.; Saladino, R.; Mincione, E. Oxidation of 2-Mercaptobenzoheterazoles by
Dimethyldioxirane. A New Method for a Synthesis of C-2 Substituted Benzimidazole,
Benzoxazole, and Benzothiazole Derivatives. Heterocycles. 1994, 38, 2621. DOI: 10.3987/
COM-94-6863. (c) Ongarora, D. S. B.; Gut, J.; Rosenthal, P. J.; Masimirembwa, C. M.;
Chibale, K. Benzoheterocyclic Amodiaquine Analogues with Potent Antiplasmodial
Activity: Synthesis and Pharmacological evaluation. Bioorg. Med. Chem. Lett. 2012, 22,
5046. DOI: 10.1016/j.bmcl.2012.06.010. (d) Yadav, V. K.; Srivastava, V. P.; Yadav, L. D. S.
Iodide Catalyzed Synthesis of 2-Aminobenzoxazoles via Oxidative Cyclodesulfurization of
Phenolic Thioureas with Hydrogen Peroxide. Tetrahedron Lett. 2018, 59, 252. DOI:
10.1016/j.tetlet.2017.12.019. (e) Simov, D.; Davidkov, K. Synthesis and IR Spectra of Some
2-Aminobenzoxazole Derivatives. Chem. Heterocycl. Compd. 1981, 17, 437. DOI: 10.1007/
BF00505682. (f) Jangid, D. K.; Guleria, A.; Dhadda, S.; Yadav, K.; Goswami, P. G.;
Khandelwal, C. L. An efficient synthesis of 2-aminobenzothiazole and its derivatives in
ionic liquids. Int. J. Pharm. Sci. Res. 2017, 8, 2960. DOI: 10.13040/IJPSR.0975-
8232.8(7).2960-64.