A. INTRODUCTION:

Chalcone compounds are -unsaturated ketone involving the reactive keto- ethylenic group (CO-CH=CH-) which gave colored compounds due to the presence (CO-CH=CH) the chromophore group. Chalcone (and related compounds “chalconoids”) is an unsaturated aromatic ketone that forms the central core for a variability of biological compound, which are known communally as chalcones. Chemically are unsaturated ketone, in a two aromatic rings are attached by a three carbon α,β-unsaturated carbonyl group. Chalcones have double conjugate bonds and a fully electric charge is distributed over more than one atom. All benzene rings are electrons.

Molecules have relatively low redox potential in the system and are more likely to undergo electron transfer reactions. The biological activity, Antiviral Activity, Anti hepatotoxic activity, Anti malarial Activity, Anti cancer Activity, Immunosuppressive Activity, Ant platelet Activity, Hypoglycemic activity, Anti inflammatory, Antibacterial Activity, etc^1-3,7

B. Preparation of Chalcone intermediate:

Mechanism of Chalcone:

In which the condensation reaction of aromatic aldehyde or ketone an aliphatic ketone or aldehyde to give a condensed product known as chalcone.⁴

1. Claisen-Schmidt condensation:

This are reaction Benzaldehyde and Acetophenone catalysed by an acid or a base followed by dehydration to yield chalcone.⁷

C₆H₅CO-CH H₂ + O=CHC₆H₅ → C₆H₅CO-CH=CHC₆H₅

Acetophenone Benzaldehyde Benzalacetophenone

Claisen Schmidt condensation reaction:

2. Aldol condensation reaction:

The first acetophenone is handled with a base such as KOH that transforms it into its enolate form, a more active form. It will then react to intermediate formation with benzaldehyde. The intermediate would then lose the molecule of water through heat to form a chalcone.⁷

3. Suzuki Reaction:

Chalcones can be prepared by Suzuki through a reaction between phenyl boronic acid and cinnamyl chloride or benzoyl chloride and phenyl vinyl boronic acid.⁷

Example

R	R¹	R²
H	H	H
H	CF₃	H
H	H	CF₃
H	NO₂	H
OMe	H	H
OMe	OMe	H

4. Fridel – Graft Reaction:

By reaction with aluminium chloride AlCl₃,⁷

Reaction through condensation between 1, 3 dimethylbenzene and 3-phenylpropanoyl chloride with AlCl₃ as catalyst, which gave high product of chalcone.

5. New Method:

Prepared chalcone by reaction through condensation between benzaldehyde and acetophenone with pyridine or pipredine as catalyst, which gave high product chalcone.⁷

6. Julia-Kocienski olefination:

2-(Benzo[] thiazol-2-ylsulfonyl)-1-phenylethanones as a new reagent for the synthesis of chalcones via Julia-Kocienski olefination with aldehydes in presence of a base in good to excellent yield of chalcones.⁵

R1 = Ph

= 4-OMePh

= 4-OCH2CH2ClPh

= 4-FPh

= 4-ClPh, etc.

7. Chalcone synthesis by Fries Rearrangement:

prepared chalcones using aryl cinnamates by Fries rearrangements catalysed by TiCl4 in moderate to good yields.⁵

R= H, 3-Me, 4-Me, 3-OMe, 4-OMe, 3-OH, 2-OMe

8. Wittig reaction:

The Wittig reaction is a powerful method for the regio- and stereo controlled construction of carbon-carbon double bonds. Wittig reaction was also used for synthesising chalcones. In these methods reaction of a stable ylide with aldehydes is used for synthesising the desired chalcone.⁵

R= H, 4-NO₂ R¹= Ph etc

A. Reactions of Chalcone:

B. Chalcone compounds can be used to preparation types of heterocyclic rings via ring closure reactions.^4,7

1. Cyclization of Chalcone with dinucleophile:

By cyclization of chalcone with diamine compounds.

a) Synthesis of Seven Membered Ring from Chalcone:

i) 2-aminobenzenethiol is reacted with chalcone undergoes acidic cyclization give 2-(4-methoxyphenyl)-4-phenyl2, 3dihydro-1,5-benzothiazepine

ii) Benzene -1, 2-diamine reacted with chalcone undergoes acidic cyclization give product 2, 4-diphenyl-2,3-dihydro-1H-1,5-bemzodiazepine

2. Cyclization of Chalcone with di amine compounds: Cyclic compounds were prepared via cyclization reaction to give pyrimidine derivatives

a) Synthesis of five Membered Ring:

i) Inpresence of guanidine chalcone convert into 4,6-diphenylpyrimidin -2-amine

ii) Chalcone recat with hydrazine give pyrazoline

b) Synthesis of Six Membered Rings

i) Inpresence of thiourea chalcone give product 4,6-diphenylpyrimidine-2(1H)thione

ii) Inpresence of urea chalcone give product 4,6-diphenylpyrimidine-2(1H) one

D. Medical Applications of Chalcone:

Chalcones and their different derivatives have been recent years. Researchers have explored new developing chalcone derivatives, which are different medicinal and biological effects.^5,6,7

1. Antiviral Activity: o-hydroxychalcone derivatives use for antiviral activity.

2) Anti hepatotoxic activity: 2 hydroxy-4-methoxy-3^’,4^’-(2”-hydroxy methyl-1”,4”-dioxano) chalcone derivatives used for hepatotoxicity.

3) Anti malarial Activity: 2, 4-dimethoxy-4’-butoxy chalcone derivatives used potent antimalerial compound.

4) Anti cancer Activity: Series of boronic chalcone used for anticancer activity.

Eg. 1) 3,5-bis-(4-boronic acid –benzylidene 1-methyl-piperidine-4-one

5) Immunosuppressive Activity: this activity is beneficial for certain autoimmune disease.

Licchalcone A and their synthetic analogues inhibit generalized lymphocyte proliferation but not restricted to any particular T lymphocyte subset.

Eg.

6) Anti platelet Activity: Arachidonic acid- induced platelet aggregation was potently inhited by all the chalcone derivatives.

7) Hypoglycemic activity: chalcone proper substitution inhibit enzyme like protein tyrosine phosphatase 1B and aldose reductase. Antioxidant property of chalcone attracted to form hybrid structure as ant hyperglycemic agent.

Dimethoxy and methylenedioxy substitution showed the best antihyperglycemic activity.

8) Antioxidant Activity: They serve in plant defense mechanism to counter act reactive oxygen species to survive and prevent molecular damage.

Eg.

9) Anti inflammatory: (2E)-1-(2,5-dimethyltetrahydrothiophen-3-yl)-3-(2-hydroxyphenyl)prop-2-en-1-one used as anti-inflammatory agent.

Eg.

10) Antibacterial Activity: Presence of reactive α,β unsaturated ketone function in chalcones responsible for antibacterial activity.

Eg.

E. CONCLUSIONS:

Chalcone derivatives are good medical applications. Synthesis of different chalcone derivatives with increase in there number of effectiveness against diseases.

These are chalcones synthesis eg. From claisen Schmidt condensation, and Aldol condensation reaction, Wittig reaction, Fridel –Graft Reaction etc.

Chalcone derivatives are mostly used in the medical application (eg. Antiviral Activity, Anti hepatotoxic activity, Anti malarial Activity, Anti cancer Activity, Immunosuppressive Activity, Ant platelet Activity, Hypoglycemic activity, Anti inflammatory, Antibacterial Activity, etc) in analytical chemistry as a reagents, and other uses.

REFERENCS:

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2. V. Calvino, M. Picallo, A.J. Lpoz Peinado, R.M. Martin-Aranda, C.J. Duran-Valle, Appl. Surface Sci. 2006; 252(17): 6071-6074.

3. M. Satyanarayana, Priti Tiwari, Brajendra K. Tripathi, A. K. Srivastava and Ram Pratap, Bioorganic and Medicinal Chemistry 2004; 12: 883-889.

4. Advanced Organic Chemistry, Reactions, Mechanisms, and Structure, Fourth edition, by Jerry March, A Wiley-Interscience Publication 939-943.

5. B. B. Chavan, A. S. Gadekar, P. P. Mehta, P. K. Vawhal, A. K. Kolsure, A. R. Chabukswar, Synthesis and Medicinal Significance of Chalcones- A Review. Asian Journal of Biomedical and Pharmaceutical Sciences, 2016; 6(56): 1-7.

6. S.Y. Hassan, "Synthesis, Antibacterial and Antifungal Activity of Some New Pyrzoline and Pyrazole Derivatives", Molecules, 2013; 18: 683-2711.

7. Aseel Mahmood Jawad, Mostafa N. Mohamed Salih, Thanaa A. Helal, Nadia Hussein Obaid, Nagham Mahmood Aljamali. Review on Chalcone (Preparation, Reactions, Medical and Bio Applications). International Journal of Chemical Synthesis and Chemical Reactions. 2019; 5(1): 16-27.

Received on 18.08.2021 Modified on 23.10.2021

Asian J. Pharm. Res. 2022; 12(2):171-175.

DOI: 10.52711/2231-5691.2022.00027