An Expedient Method for the Synthesis of 1,2,4-Triazolo-fused
1,5-Benzodiazepine, 1,5-Benzoxazepine, and 1,5-Benzothiazepine
Scaffolds: A Novel Seven-membered Ring System of Biological Interest
Vo l 5 5
and Bhawani Singh
Department of Chemistry, JECRC University, Jaipur, Rajasthan 303905, India
Department of Chemistry, Banasthali Vidyapith, Banasthali, Rajasthan 304022, India
Department of Pure & Applied Chemistry, University of Kota, Kota, Rajasthan 324005, India
Received May 29, 2017
Published online 4 January 2018 in Wiley Online Library (wileyonlinelibrary.com).
New heterocyclic compounds 1-(3-methyl-9H-dibenzo[b,f][1,2,4]triazolo[4,3-d][1,4]diazepin-6-yl)
ethanone 8a, 1-(3-methyldibenzo[b,f][1,2,4]triazolo[4,3-d][1,4]oxazepin-6-yl)ethanone 8b, and 1-(3-
methyldibenzo[b,f][1,2,4]triazolo[4,3-d][1,4]thiazepin-6-yl)ethanone 8c are synthesized from benzodiazepinone,
benzoxazepinone, and benzothiazepinone derivatives. These heterocyclic scaffolds have wide medicinal
importance. Best results were obtained in antibacterial screening against Escherichia coli, Enterobacter
cloacae, and Staphylococcus aureus and antifungal screening against Candida albicans and Fusarium
oxysporum. 1,1-Diphenyl-2-picrylhydrazyl radical scavenging activities of compounds 6c, 7c, and 8c were
tested in doses 10, 20, 30, 40, and 50 μg/mL and were expressed as IC
values and percent of inhibition
with means ± standard deviation of three different concentrations of synthesized compounds. The
assignment of the structures of synthesized compounds was made by thin-layer chromatography, elemental
C-NMR, and liquid chromatography–mass spectrometry.
J. Heterocyclic Chem., 55, 586 (2018).
Privileged scaffolds of benzodiazepine derivatives with
huge pharmacological importance are exclusively
suitable for the preparation of molecular libraries of
and trizolo[1,5]benzothiazepines. The triazole and
azepine derivatives are the valuable synthons for drug
discovery because of their high pharmacological proﬁles
compared with other heterocyclic ring systems. These
heterocyclic derivatives also identify potent and selective
binders for multiple biological targets from a library.
These heterocycles are crucial pharmacophores for a
variety of important chemical products, materials,
pharmaceuticals (e.g., triazolam, alprazolam, etizolam,
midazolam, and adinazolam) [1–3], and agrochemicals .
These triazole-condensed heterocyclic derivatives hold
many medicinal applications like potent sedative, muscle
relaxant, depression, psychoactive drug, hypnotic,
anticonvulsant, antibacterial, and antifungal activities [5–9].
On the basis of importance of heterocyclic compounds
herein, we report a protocol for the synthesis
diazepin-6-yl)ethanone 8a, 1-(3-methyldibenzo[b,f][1,2,4]
triazolo[4,3-d][1,4]oxazepin-6-yl)ethanone 8b, and 1-(3-
yl)ethanone 8c derivatives aimed at deﬁning their
pharmacological roles. Research in this area is still very
active and is directed toward the synthesis of
compounds with enhanced pharmacological activities.
RESULTS AND DISCUSSION
The synthetic route, which is applied for the synthesis of
target triazolo derivatives 8a–c, is outlined in Scheme 1. It
is not surprising, therefore, that there has been a signiﬁcant
and ever increasing interest in the design and synthesis of
this class of heterocyles. 1-(4-chlorophenyl)ethanone 1
 was treated with fuming HNO
1-(4-chloro-3-nitrophenyl)ethanone 2 . Compounds
4a–c were obtained via the application of Ullmann
condensation reaction on heating of 1-(4-chloro-3-
nitrophenyl)ethanone 2 and 3a–c (2-aminobenzoic acid,
2-hydroxybenzoic acid, or 2-mercaptobenzoic acid) with
potassium carbonate, Cu, CuI, and nitrobenzene . The
Ullmann condensation was reported by Irma Goldberg
 where copper was used as a catalyst for ether
linkage. Ullmann reaction has been used in the
preparation of various classes of heterocyclic compounds
like benzodiazepines, benzoxazepines, benzothiazepines,
benzothiazepinones, and triazolo-fused derivatives.
Compounds 4a–c undergo selective reduction of aromatic
nitro group into amine group following by Fe powder
and HCl in aqueous ethanol  and provide us amino
derivatives 5a–c. Compounds 5a–c subsequently undergo
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