INTRODUCTION

INTRODUCTION OF CHALCONES:-

“Chalcone” is derived from the Greek word “chalcos”, meaning “bronze”, which results from

the colors of most natural chalcones. Chalcone compounds have a common chemical scaff old of

1,3-diaryl-2-propen-1-one, also known as chalconoid, that exists as trans and cis isomers, with

the trans isomer being thermodynamically more stable.

The chalcone family has attracted much interest not only from the synthetic and biosynthetic

perspectives but also due to its broad interesting biological activities. Therapeutic applications of

chalcones trace back thousands of years through the use of plants and herbs for the treatment of

diff erent medical disorders, such as cancer, inflammation, and diabetes. Several chalcone-based

compounds have been approved for clinical use. For example, metochalcone was once marketed

as a choleretic drug, while sofalcone was previously used as an antiulcer and mucoprotective

drug

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 CHALCONES FROM NATURAL SOURCES

Chalcones are the core of many biologically interesting compounds from natural sources and

have attracted substantial research attention for decades. How many natural chalcones have been

isolated and structurally elucidated? The answer to this question depends on how broadly the net

is cast. As in many articles, the term “chalcone” refers generically to chemicals with an α,β-

unsaturated ketone system. Thus, the chalcone family has extensive structural diversity and can

be roughly classifi ed into two categories: simple/classical chalcones and hybrid chalcones with

the core scaff old of 1,3-diaryl2-propen-1-one. Bichalcones, such as rhuschalcone from Rhus

pyroides, contain two chalcone moieties in a single structure. 23 Dihydrochalcones, such as the fl

eminchalcones from Flemingia philippinensis, are a class of compounds with a reduced α,β- 24

unsaturated double bond. Chalcone mimics (e.g., piperlongumines ) and fused chalcones (e.g.,

oxyfadichalcones ) are not structurally traditional chalcones, although they have a similar α,β-

unsaturated ketone system or fused forms derived from chalcones by special biosynthesis

pathways. When searching for the classical chalcone in the well-known chemical databases,

more than 92 000 chalcones can be found in SciFinder and over 1000 of them have biological

data reported in PubChem Therefore, the number of natural chalcones may ultimately not be

countable with certainty. Representative classical chalcones, bichalcones, dihydrochalcones,

chalcone mimics, and fused chalcones isolated from natural sources in recent years and their

potential biological activities are summarized in Table 1. Some of their biological activities and

applications will be discussed in the following sections.

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TABLE 1:-

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 Review of literature

Chalcone is synthesized by Claisen-Schmidt condensation, which involves the cross-aldol

condensation of aldehydes and ketones with a base or acid catalyst followed by a dehydration

reaction. Chalcone is a common natural pigment and one of the important intermediaries in

flavonoid biosynthesis . In laboratory synthesis chalcone can be made using the Claisen-Schmidt

reaction by reacting acetophenone compounds or their derivatives with benzaldehyde or their

derivatives using strong bases such as NaOH, KOH, Ba(OH)2, LiOH.2H2O or NaH as catalysts

in polar solvents. Other catalysts that can also be used are sodium phosphate and aluminum-

magnesium hydroxide hydrate. Whereas acid catalysts are usually used such as HCl, AlCl3, BF3-

Et2O, TiCl4, RuCl3 . Recently, there have been many synthetic studies involving chalcone

compounds. From previous research conducted by chalcone synthesis was carried out without

the use of solvents, this method produced very high product yields. In the study benzaldehyde

and acetophenone were used in the presence of solid NaOH in mortars, with large crude product

yields ranging from 81-94%. In 2014 it was reported that chalcone compound (1,3-diphenyl-2-

propen-1-one) and its derivative 4-methoxychalcone could be synthesized by microwave

irradiation (400 watt power for 9 minutes) with a catalyst acid (bentonite/montmorillonite) and

yield percentage of 1.72% and 5.21%. Several years the synthesis of several chalcone

derivatives was reported by using two methods, namely the conventional method and the

microwave irradiation method.

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 OBJECTIVE

The main objective of the project is to synthesize Chalcone via Claisen Schmidt condensation

and its structure determination by using H1 NMR and C13 NMR spectra. As already mentioned ,

chalcone and its derivatives possesses remarkable biological activity and pharmacological

activities so in this project we have tried to synthesize this compound.

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 SYNTHESIS OF CHALCONE

 Chalcone synthesis different approach

The following paragraphs describe some of the important synthesis of chalcones by

using different chemical reactions other than Claisen Schmidt reaction.

By Wittig reaction

By Julia Olefination

By Heck Reaction

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Suzuki−Miyaura Coupling for Chalcone Synthesis

One-Pot Synthesis of Chalcones

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  Claisen−Schmidt Condensation: Overview

The Claisen−Schmidt reaction is named after two pioneering investigators, R. L. Claisen and J.

G. Schmidt, and describes a process in which a benzaldehyde and a methyl ketone are condensed

in the presence of catalysts

The reaction between an aldehyde or ketone having an alpha-hydrogen with an aromatic

carbonyl compound lacking an alpha hydrogen is called the Claisen–Schmidt condensation. - In

cases where the product formed still has reactive alpha hydrogen and a hydroxide adjacent to an

aromatic ring, the reaction will quickly undergo dehydration leading to the condensation product.

Mechanism of the reaction:-

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This reaction is deemed one of the most classical reactions in Organic chemistry. The catalysts

are either strong bases or acids. In the case of base catalysis, the chalcone is generated from the

aldol product via dehydration in an enolate mechanism, while in the case of acid catalysis, it is

generated via an enol mechanism. The main drawback of this reaction is the slow reaction rate;

the reaction typically needs several days for completion. The reaction could also result in a

complex mixture containing the desirable product, byproducts, and sometimes starting materials.

The yield therefore could vary dramatically, depending on the reactants and catalysts, ranging

from <10% to near 100% conversion. Nevertheless, this reaction has been employed in most

publications because of its experimental simplicity and highly efficient formation of the

carbon−carbon double bond with little restriction to the complexity of the molecules. Szell and

co-workers synthesized a series of nitrochalcones and showed that the presence of electron-

donating groups in the aldehyde favored condensation by acids, while electron-withdrawing

substituents favored condensation by base conditions. Generally, the base condition is more

common in chalcone synthesis.

Base Condition:- The classical Claisen−Schmidt condensation is base-catalyzed with potassium

tert-butoxide, sodium hydroxide, or potassium hydroxide in methanol or ethanol at room

temperature. This reaction has been widely used for the synthesis of hydroxyl-substituted

chalcones, typically with good to excellent yields (60−90%). A group of ferrocenyl chalcones

has been synthesized under the common base (sodium hydroxide) condition In some cases, an

increase in temperature is required, and the base condition also requires modifi cation. For

example, the α-carbon of a ketone is difficult to dehydrate when the ketone is electrophile

substituted. Such a reaction requires refl ux at an elevated temperature or takes a longer time at

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room temperature. However, with a nucleophile substitution on the α-position, mild conditions

are generally sufficient

Acid Condition:- Although base catalysts are generally used for the synthesis of chalcones,

Brønsted acids, Lewis acids, and solid acids have also been utilized as acid catalysts. The most

common application using ethanol saturated with the Brønsted acid HCl is marginally successful,

with only a 10−40% yield. Dry HCl gas has been shown to be more favorable to the reaction

because it acts as not only a catalyst but also a water absorbent. Aluminum chloride (AlCl3) has

also been used as a Lewis acid for chalcone synthesis. Two moles of acetophenone per mole of

AlCl3 provide the chalcone product in a high yield (73%). The mechanism of the reaction is not

simply the result of the hydrogen chloride evolved by the heating of acetophenone and AlCl3; an

intermediate of the general type of R−O−Al−R2 actually promotes the condensation. The

application of boron trifl uoride−etherate (BF3−Et2O) in the condensation was fi rst reported in a

study describing the use of BF3 gas in chalcone synthesis. In 2007, Narender et al. reported the

use of BF3−Et2O to obtain 15 chalcones with 75-96% yields with reaction times of less than 3 h.

Petrov et al. reported that 16 chalcones, including 4- hydroxyl-chalcone were synthesized in a

SOCl2/ethanol system in high yields (73−96%). SOCl2 was used as a convenient alternative to

the gaseous HCl in the condensation, where HCl was generated in situ by the reaction of SOCl2

with absolute ethanol.

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 IMPORTANTANCE OF CHALCONE

1. The presence of α, β- unsaturated carbonyl system of chalcone makes it biological active.

They have shown antibacterial activity against S. aureus , E.coli etc and some other

organisms.

2. Chalcones and their derivatives find various application as artificial sweetners ,

polymerization catalyst , fluorescent , whitening agent , organic brightening agent ,

stabilizer against heat etc.

3. Preclinical studies on chalcones and their derivatives have shown their high potential as

antidiabetic , anticancer , anti-inflammatory, antimicrobial, antioxidant , antiparasitic,

psychoactive and neuroprotective agent.

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 RESULT AND DISCUSSION

 Experimental section
General information:-

All the commercially available reagents were used as received. Melting points were

measured with a melting point apparatus and are uncorrected. NMR spectra were recorded on

Brucker 400 MHz FT-NMR spectrometer using tetramethylsilane (TMS) as an internal standard.

All experiments were monitored by thin layer chromatography (TLC). TLC was performed on

peractivated self prepared pltes with silical gel-G. After elution, plate was visualized in iodine

chamber.

Synthesis of Chalcone:-

The experiment was started by adding 5 mmol of acetophenone into 5 ml of ethanol in a

round bottom flask, then 5 mmol of benzaldehyde was added to the flask. Then to the mixture

was added 60% NaOH solution, the NaOH is added dropwise while stirring with a stirrer. After

adding NaOH the mixture was stirred for 1.5 hours at room temperature. After mixing, the

mixture is allowed to stand for 4 to 6 hours at room temperature. After being allowed to stand for

up to 6 hours the mixture was poured into ice cold water. Then the crude product formed is

filtered and washed with water. Finally pure chalcone is obtained by recrystallisation with

ethanol.

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A series of chalcones have been prepared by using differently substituted aromatic aldehydes.

The results are summerised in the following table. The structure of the end product is confirmed

by spectral analyses

Sl No R Product Yield(%)
1 H 3a 85
2 4-Cl 3b 84
3 4-CH3 3c 86

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  SPECTRAL ANALYSIS

Sample 1

H-NMR (400 MHz, CDCl3)

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 C-NMR (101 MHz, CDCl3)
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Spectral data of the compound 3a1,3-diphenyl-2-propen-1-one

Yellow solid; mp 145 −147 0C (d); 1H NMR (400 MHz, CDCl3) δH, 8.03 (d, 1H, CH), 8.01-7.43
(m, 10H, aromatic) 7.53 (d, 1H, CH). 13C NMR (100 MHz, CDCl3) 190.67, 144.9, 138.2, 134.9,
132.9, 130.6, 129.0, 128.7, 128.6, 128.5, 122.14.

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 CONCLUSION:-

 In conclusion, the present method disclose a new and simple method for the

synthesis of chalcone using claisen Schmidt condensation. The base catalyst

synthesis of chalcone is simple, high yielding and environment friendly, In

addition to this its simplicity,salient features like product isolation by simple

filtration and non generation of side products constitute a useful alternative to the

commly accepted procedures chalcones and their derivatives have attracted

increasing attention of scientists for the search of new potent pharmacological

activity in it.

 From the experimental process we have got some practical knowledge about

chalcone synthesis, their spectral analysis and get the opportunity to apply our

theoretical knowledge.

 We also know how to do literature review in a project work.

We also learnt about research methdology

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