Synthesis and Biological Activities of Carbazole-Thiazole based Schif

base Derivatives
By

Iqra Yasin

1) Registration #: CHEM231501035

2) Degree Program: MS Chemistry

3) Department: Institute of Chemistry

4) Faculty: Faculty of Natural and Applied Sciences

5) Supervisor Name: Dr. Madiha Irfan

6) Co-supervisor Name (if any): NA

7) Degree Enrollment Semester: Fall 2023

8) First Time Thesis/Dissertation Enrollment Semester: 3rd

9) Freezed or Missed Semester: NA

10) Semester in Which Supervisor was Allotted: 3rd

11) Expected Thesis Completion Semester: 4th

12) Date of Synopsis Submission to the Department: 02-7-2024

13) Date of Approval from DGRC: ------------------------------------------------------------

Scholar’s Signature Supervisor’s Signature Signature of the Convener DGRC

Signature of the Coordinator BASR

Date of submission to the Directorate of BASR:
----------------------------------------------------

Date of Approval by BASR: ---------------------------------------------------------------------------

1. Description of the Research Work

Recently, there has been a lot of interest in designing and synthesizing new
physiologically significantchemical molecules..(Gomtsyan, 2012; Lemilemu, Bitew,
Demissie, Eswaramoorthy, & Endale, 2021).Although more than 60% of organic
compounds are heterocycles with numerous applications, the number of functionalized
and easily available heterocyclic compounds is limited.(Lemilemu et al., 2021).
Schiff bases are chemicals that are commonly utilized in medicine, pharmaceuticals, and
industry.(Yadav, Sarkar, & Kumar, 2019).These are generated by reacting an active
carbonyl group with a primary amine to produce imine derivatives. The general formula
for Schiff base is RCH=NR..(Yadav et al., 2019).A wide range of Schiff base compounds
can be produced and explored due to their flexible and distinctive structures. Schiff bases
are often utilized as starting materials to generate different amino acids. They also
demonstrate a number of pharmacological applications such as antibacterial, anticancer,
anti-inflammatory, and ant diabetic.(Al-Labban, Sadiq, & Aljanaby, 2019; Mishra,
Ghanavatkar, Mali, Chaudhari, & Sekar, 2019; Raju et al., 2022).
Heterocycle-containing schiff bases offer unique and adaptable uses as well. In the
biomedical business, heterocycles are regarded as the most significant component of both
commercially available medications and novel drug discovery(Elmorsy, Eltoukhi, Fadda,
Abdel-Latif, & Abdelmoaz, 2023).Heterocycles are primarily composed of nitrogen,
sulfur, and oxygen; however, the carbazole and thiazole moieties are also highly
significant.(Gomtsyan, 2012)With their diverse molecular structures, thiazole and
carbazole are employed in optical, medical, and electronic fields.(Durgun et al., 2020;
Suyambulingam et al., 2020).Organic heterocyclic compounds such as carbazole and
thiazole are utilized as natural medicinal molecules and building blocks for synthesis.
(Elmorsy et al., 2023).
Carbazoles are heterocyclic aromatic compounds that possess a large conjugated
structure. They are composed of two six-membered pyrrole rings joined with a five-
membered nitrogen ring(Ziarani, Moradi, Lashgari, & Kruger, 2018).With a broad range
of biological activities, such as antimalarial, antibacterial, and anticancer activity, the
carbazole scaffold is present in many bioactive natural products and synthesized
compounds(Maji, Kumar, Kaulage, Muniyappa, & Bhattacharya, 2014; S Tsutsumi,
Gündisch, & Sun, 2016). Furthermore, carbazole compounds exhibit cytotoxicity and
anticancer action towards cancer cells. H8).(Li et al., 2018)
Furthermore, carbazole compounds exhibit cytotoxicity and anticancer action towards
cancer cells. H8) Thiazole is five-membered rings with the chemical formula C3H3NS,
one sulfur and one nitrogen atom each. Thiazole rings are essential in natural compounds
like coenzyme carboxylase and vitamin B1.(Saydam & Alkan, 2001)..It has several
biological uses, including anti-inflammatory, anti-mycobacteria, anti-cancer, anti-
 microbial, and antiviral properties.(Elmorsy et al., 2023)..Its anti-tuberculosis and
fungicidal hypothermic properties are also present. Studying the thiazole moiety complex
is hence intriguing. The combination of thiazole and carbazole derivatives in a schiff base
will demonstrate the broad characteristics of both compounds also and enhance its
biological and optoelectronic properties. In the present work, we create a novel series of
schiff base derivatives using aromatic aldehyde and amine based on carbazole and
thiazole to create a highly conjugated system and study their biological and antimicrobial
activities.
2. Need and Significance of the Research
Schiff bases are a significant class of ligands that are produced when an amine and an
aldehyde react. The C-N bond in azomethine is useful for its biological activities, and its
derivatives with heterocyclic compounds also exhibit remarkable antibacterial, antifungal,
anticancer, and antiviral, antimalarial activities.(Yadav et al., 2019). Schiff bases are
employed as starting material and in the synthesis of complex molecules.
In addition, they possess optical and magnetic properties. Their combination with zinc is
usually employed in the production of light-emitting diodes and fluorescent and
electroluminescent devices. The synthesis of carbazole and thiazole-based Schiff bases is
a novel approach that has been used recently to create a noval molecule.
A significant class of natural chemicals with antioxidant qualities are carbazole alkaloids,
due to their intriguing biological and antioxidant effects.((Hieda et al., 2014)).
Furthermore, the usage of carbazole-based compounds in organic solar cells is
particularly significant because to their strong hole transfer feature, significantly
improved photoconductivity, thermal stability, and presence of electrons. The anticancer
activity profiles of compounds containing thiazole exhibit a variety of mechanisms
(Gomha et al., 2021).The thiazole moieties, which are important pharmacological
scaffolds, are responsible for the potent anticancer, bactericidal, anti-HCV9, and anti-
inflammatory effects of their heterocyclic compounds. Optoelectronic applications may
improve from thiazole strong charge carrier property. Its structure is electron-deficient,
which also demonstrates oxidative stability. ((Reginato, Mordini, Zani, Calamante, &
Dessì, 2016)).Accordingly, in order to build a novel molecule with a wide range of
biological and antibacterial applicability, we shall generate schiff bases based on
carbazole and thiazole.

2.1: Research Objectives

Schiff bases are important class of ligand and had wide pharmacological,biological and
optoelectronic applications.Additionally the attachment of highly conjugated carbazole and
thiazole derivatives also increased its activity.
The general objectives of this research are:
i) To synthesize novel carbazole thiazole based schiff base derivatives.
ii) To perform the spectroscopic (FT-IR, NMR, UV-Vis), of novel schiff base
derivatives.
iii) To study its biological activities mainly antimicrobial properties.
3. Review of Literature:
Mohamed R.Flmorsy synthesized nine derivatives of carbazole linked thiazolidinone by
reacting several derivatives of thiazolin-4-one and thiazolin-5-one with 9-ethylcarbazole-
3-carbaldehyde . Mass spectrometry, proton and 13C NMR, and infrared spectroscopy
were among the spectroscopic techniques used to confirm the structures of these
compounds. These derivatives' cytotoxicity against breast cancer was assessed, and it was
confirmed that artificial Thiazole compounds can be used as potent anticancer medication
inhibitors. (Elmorsy et al., 2023)
Fitsum Lemilemu synthesized five derivatives of thiazole-based Schiff bases by changing
the benzaldehyde and acetophenone phenyl ring substituents and reacted it with anime
derivatives thiourea, phenyl thiazole and p.nitro acetophenone thiazole. By using silica
Gel column chromatography and recrystallization, the produced compounds were
purified.The produced substances exhibited moderate to strong antioxidant and
antibacterial properties. As compared to the conventional method, ZnO nanoparticles
were discovered to be a very effective catalyst in the green synthesis strategy, which was
found to be a very effective way to create biologically active molecules. This approach
also had substantial pharmacological potential, as it could modify the activity of
numerous enzymes involved to metabolism. Combining many spectroscopic techniques
(13C NMR, proton NMR, FT Infrared spectroscopy, and UV-Visible spectroscopy)
allowed researchers to determine the structures of the produced substances. (Lemilemu et
al., 2021)
Mahamadhanif S. Shaikh synthesized various substituted carbazole-thiazole compounds
by using molecular hybridization method. In this research a novel compounds of thiazolyl
substituted with carbazole hydrazine analogues was synthesized by carbazole ring
N.methylation in the presence of iodo methane and NaH..Further, This product undergone
a Vilsmayer Hack formylation process using DMF and POCL3 to yield 9-methyl-
carbazole-3-carbaldehyde, which, in the presence of glacial acetic acid l and
methanol ,interacted with thiosemicarbazide to produce 1-((9-methyl-carbazol-6-yl
Methylene)thiosemicarbazide. To obtain the end product, above compound undergoes a
Hantzsch cyclo-condensation reaction with different properly substituted α-
heteroaromatic ketones using methanol. The structure and properties of above
intermediate compound and its associated thiazolyl substituted with derivatives of
carbazole hydrazine were determined by using spectral (Infrared spectroscopy,HRMS,
C13-NMR and proton NMR) and physicochemical data. Additionally, the
antimycobacterial activity and in vitro cytotoxicity profile were examined.(Palkar, Rane,
Alwan, &Hampannavar)
Peng-Hui Li synthesized derivatives of carbazole composed of Chalcone analogs to study
its cytotoxicity and Topo II inhibition activity. In this method carbazole N-alkylation was
processed out using KOH and benzyl bromides .Then to synthesize N-subsititued-9H-3-
carbaldehydes. the formylation of above product was carried out . Further suitable
acetophenone undergone aldol condensation in the presence of basic medium of sodium
hydroxide .Then to obtain benzyl substituted N- carbazole substitution on phenyl rings
was carried out to study its cytotoxicity and TOPO II inhibition activity. (Li et al., 2018)
Magdalena Barwiolek synthesized two macro cyclic Schiff bases using obtained from 2-
hydroxy-5-tert-butyl-1, 3-benzenedicarboxaldehyde L2,o-phenylene diamine and 2-
hydroxy-5-methylisophthalaldehyde L1. The above compounds were characterized by
UV-visible spectroscopy, Infrared spectroscopy, X-ray crystallography and fluorescence
spectroscopy. The optical properties of Schiff bases and its compound obtained by using
o-phenylenediamine were also examined by these techniques. (Osmaniye et al., 2018)
Sobhi M Gomha produced a significant method to develop an advance and new
anticancer treatment using a hybrid method.In this process a novel compounds of 5-(1-
(2-(thiazol-2-yl) Hydrazono) ethyl) thiazole was synthesized by using 1-(4-Methyl-2-(2-
(1-(thiophen-2-yl) ethylidene) hydrazinyl) thiazol-5-yl) ethanone as starting material .The
activity of this compound was investigated for MCF-7 tumor cells with the help of MTT
assay (Gomha et al., 2021)
Yuhzo Hieda synthesized eight compounds carbazomadurins and carazostatin its
precursors and carquinostatin, carbazomadurin B and their precursor to study the
antioxidant activity of alkaloid of 3,4-dioxygenated and 3- oxygenated carbazole These
substances have demonstrated their value as helpful idea in the creation of novel
antioxidants. (Hieda et al., 2014)
Derya Osmaniye synthesized noval sixteen derivatives of 2-(benzothiazol-2-ylthio)-N -
(3-substituted-4-(3,4-substitutedphenyl)thiazol-2(3H)-ylidene) acetohydrazide.The
structures of the synthesized compounds were elucidated using HRMS, FT-infrared
spectroscopy, proton NMR and C-13 NMR spectroscopy. By triggering apoptosis, the
synthesized substances exhibit anticancer activity.(Osmaniye et al., 2018).
4. Research Methodology
In this method, we synthesized a carbazole thiazole derivative of schiff base .It is
basically a four step synthesis of schiff base.In the firststep, alkylation of 9-carbazole take
place with octyl iodide to give 9-octyl carbazole.

Then the 3, 6 di acylation of the above compound is achieved by Friedel craft acylating
agent .This product is then react with thiourea in the presence of iodine to attach thiazole

on 3 and 6 position of carbazole to generate a heterocyclic carbazole thiazole based amine

which then react with derivative of aromatic aldehyde by condensation reaction to yield a
novel carbazole thiazole based schiff base derivative.
Characterization
Synthesized compound will be characterized by different spectroscopic techniques.
1. UV-Visible technique
2. Infrared spectroscopy
3. Mass Spectrometry
4. NMR spectroscopy

5. Expected Outcomes of the Research

 The synthesized product can be useful compound and have wide biological properties
and can be used to synthesize various compounds as a starting material.

6. References
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7. Appendix
7.1: TURNITIN Originality Report (Attach with signature of supervisor and
student)

Turnitin Originality Report

Tested on 27 June, 2024, by Turnitin Anti Plagiarism Software Provided by Higher

 Education Commission, Pakistan to the Instructor of the KFUEIT, RYK, Punjab,
Pakistan.

Synopsis Title: Synthesis and Biological Activities of Carbazole-Thiazole based Schiff

Based Derivatives

Scholar’s Name: Iqra Yasin

Institution: KFUIET, RYK, Punjab, Pakistan