Research Statement
1. Title of the project
Synthesis of Heterocyclic Compounds and their applications in medicinal chemistry
2. Applicant
Gibran Umar Khan
3. Research Program
5.1 Introduction
A heterocyclic substance with a five-membered ring made up of two nitrogen atoms and one
oxygen atom is called oxadiazole. Oxadiazole-ringed compounds have been investigated for
biological properties including tyrosinase inhibition, antiviral, antibacterial, anticancer,
antihypertensive, neuroprotective, and anticonvulsant action [1]. A preferred scaffold, 1,2,4-
oxadiazole is present in a wide range of bioactive compounds, medications, and functional
materials [2]. They are frequently referred to as amides and esters' bio isosteres [3].
One of the often-occurring substructures in a wide range of medicines, synthetic intermediates,
and physiologically active chemicals is oxazoles. Highly substituted oxazole derivatives have been
efficiently and quickly synthesized using a variety of synthetic techniques. The three main
components of traditional oxazole synthesis processes are the oxidation of oxazolines, the
cyclization of acyclic precursors, and the C-C coupling of oxazoles with other reagents [4]. Many
natural products contain these essential biological scaffolds [5]. Chemists have explored one of
the convenient routes of synthesis of heterocyclic compounds by utilizing amide functionality as
a starting precursor [6].
Amides are undoubtedly one of the most significant functional groups in organic chemistry due to
their incorporation in a variety of intriguing molecules, including peptides, pharmaceuticals,
naturally occurring chemicals, proteins, and alkaloids. [7]. They are among the most important
bond connections in substances and materials that are pharmacologically active [8]. Amides are
increasingly used in a variety of synthetic transformations as catalysts, ligands, reagents, solvents,
and substrates [9]. Due to the strong bond polarity and durability, they are present everywhere in
nature as the foundation of proteins and can also be found in high-value items like medications
and polymers [10].
Natural materials frequently contain scaffolds called oxindoles, and they also offer useful
pharmacological lead compounds [11]. Many natural compounds and synthetic counterparts with
a wide range of biological functions have the oxindole motif. The numerous reviews devoted to
various areas of oxindole synthesis are another indication of the considerable interest in these
heterocycles [12].
5.3. Methodology for the synthesis of heterocyclic compounds starting with amide
Scheme. 1. Electrophilic cyclization reactions from amides [13]
There are variety of routes for synthesis of heterocyclic compounds starting with amide. The
scheme 1 represent the synthesis of heterocyclic compounds through electrophilic cyclization of
amide.
Proposed Scheme
Scheme 2. Synthesis of triazoles from 4-methoxybenzohydrazide and Phenyl isothiocyanate [14]
4. Significance of Study
Heterocyclic compounds have a wide spectrum of biological activities and pharmaceutical
potential. By synthesizing the new heterocyclic compounds and their derivatives we are aiming to
explore new routes and greener methods wherever possible. This will be contributing to the
scientific community and stakeholders by exploring their applications.
References
1. Kuram, M. R., Kim, W. G., Myung, K., & Hong, S. Y. (2016). Copper‐Catalyzed Direct
Synthesis of 1, 2, 4‐Oxadiazoles from Amides and Organic Nitriles by Oxidative N–O
Bond Formation.
2. Young, J. R., & DeVita, R. J. (1998). Novel synthesis of oxadiazoles via palladium
catalysis. Tetrahedron letters, 39(23), 3931-3934.
3. Glöckner, S., Tran, D. N., Ingham, R. J., Fenner, S., Wilson, Z. E., Battilocchio, C., & Ley,
S. V. (2015). The rapid synthesis of oxazolines and their heterogeneous oxidation to
oxazoles under flow conditions. Organic & biomolecular chemistry, 13(1), 207-214.
4. Zheng, M., Huang, L., Huang, H., Li, X., Wu, W., & Jiang, H. (2014). Palladium-catalyzed
sequential C–N/C–O Bond Formations: Synthesis of oxazole derivatives from amides and
ketones. Organic letters, 16(22), 5906-5909.
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Simple synthesis of amides via their acid chlorides in aqueous TPGS-750-M. Organic
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Green Chemistry, 21(13), 3675-3681.
10. Sayes, M., & Charette, A. B. (2017). Diphenylsilane as a coupling reagent for amide bond
formation. Green Chemistry, 19(21), 5060-5064.
11. Luan, X., Wu, L., Drinkel, E., Mariz, R., Gatti, M., & Dorta, R. (2010). Highly chemo-and
enantioselective synthesis of 3-Allyl-3-aryl oxindoles via the direct palladium-catalyzed α-
arylation of amides. Organic letters, 12(9), 1912-1915.
12. Luan, X., Wu, L., Drinkel, E., Mariz, R., Gatti, M., & Dorta, R. (2010). Highly chemo-and
enantioselective synthesis of 3-Allyl-3-aryl oxindoles via the direct palladium-catalyzed α-
arylation of amides. Organic letters, 12(9), 1912-1915.
13. Slivka, M., & Korol, N. (2022). Synthesis of mononuclear heterocycles via electrophilic
cyclization. Monatshefte für Chemie-Chemical Monthly, 153(1), 1-8.
14. Shah, S. A. A., Ashraf, M., Rehman, J., & Saleem, R. S. Z. (2018). Synthesis, in vitro and
in silico studies of s-alkylated 5-(4-methoxyphenyl)-4-phenyl-4H-1, 2, 4-triazole-3-thiols
as cholinesterase inhibitors. Pak. J. Pharm. Sci, 31(6), 2697-2708.
