Gaikwad 16042012

-:INTRODUCTIONINTRODUCTION:-

1Shri Shiv Chhatrapati College, Junnar

-:INTRODUCTION :-Coumarin is first identified in 1820, and is an oxygen heterocyclic

compound famous for its vanilla like or freshly mowed hay fragrance.

Coumarin contains benzene ring and a α-pyrone fused together. Coumarin is

generally found in many plants like tonka seeds, sweet clover grass, lavender

and licorice. It is also present in fruit bearing plants like apricots, cherries,

strawberries and cinnamon.

Artificial production of Coumarin started since 1820 and has been used in

manufacture of flavoring and perfume since 1868. Coumarin is produced as

pesticides by the plants and artificially it is used to manufacture amalgams like

anti coagulants and rat poison. Coumarin is the responsible for the smell mown

grass and hay. When Coumarin is fermented it generates dicoumarol which

present in sweet clover. This is very strong anticoagulant which forms base of

rat poison, which creates hemorrhage in the rodents. This discovery in modern

days scientists used as anti clouting agent.

Coumarin has appetite suppressing properties, suggesting its wide spread

occurrence in plants, especially grasses, because of its effect of reducing impact

of grazing animal. Coumarin often found in tobacco and artificial vanilla

substituents. Coumarin has been used in the treatment of lymph edema.

Coumarin used in toxicity and used in foods, beverages, tobacco and cosmetics.

Some natural additives containing Coumarin e.g. sweet woodruff are used in

alcoholic beverages. In Europe such beverages are very popular f or example

maiwein (white wine with woodruff) and zubrowka (wodka flavor with bison

grass). Coumarin is also used in flavoring additive in pipe tobacco. Coumarin

possesses anti bacterial properties hence it is used to cure goat fever.

There are several byproducts of Coumarin they include antifungal

umbelliferrone present in umbelliferae or aromatic plant family and in many


other exclusive medicines. Berapten obtain from bergamot oil applied as

sunscreen agent in many suntan lotions.

Asculatin is obtaining from horse chest nut (aesculus hippocastanum) as

precious vascular therapeutic agent. Coumarin and all its derivative are

considered as phenyl propanoids.

Similarly coumarin derivatives have been of great interest because of

their role in natural and synthetic chemistry. Many products which contain a

coumarin subunit exhibit biological activity such as molluscicides, anthelmintic

hypnotic insecticidal activity and some are serving as anticoagulant agents and

fluorescent brighteners. So coumarins containing a Schiff base are expected to

have enhanced antitumor and other biological activities. It is well established

that the biological activity associated with the hydrazones compounds attributed

to the presence of the active pharmacophore. Hence many hydrazones

compounds containing this active moiety showed good anticancer bioactivities

according to the literature.

Microwave radiation of organic reaction has rapidly gained popularity as

it accelerates the reaction towards a variety of synthetic transformation, solvent

less procedures without the use of supporting reagents and hence eco-friendly.

Chemical transformations that took hours or even days to complete can now be

accomplished in minutes. Microwave energy offers numerous benefits for

performing synthesis such as increased reaction rates, enhanced yields and

cleaner chemistries. Hence, in this paper, we are reporting the synthesis of

coumarin analogues with Schiff bases and hetero aromatic aldehydes by

conventional and microwave assisted methods, and their characterization

through spectral data such as IR, 1HNMR and Mass spectra. Their antimicrobial

activity was also evaluated.


Some derivatives of coumarin as follows :-

Sr.No Structure Derivative Name

12[(4-methyl-2-oxo-2Hchromene-6-yl) oxyl) acetic acid.

2Ethyl-7-hydroxy-2-oxo-2h-chromene-3-carboxylate.

3 7-hydroxy-4-methyl-2-oxo-2h-chromene-8-yl acetate

4 8-acetyl-6-hydroxy-7-methoxy-2oxo chromene

5 5-Bromo-7-methoxy-4-methyl-2-oxo-2h-chromene


Chemistry of 7-Methoxy-4-Methyl-2-Oxo-Chromene-6-Carbaldehyde:-

1) Structure :-

2) Molecular formula: - C12H10O4

3) Nature: - Yellow solid

4) Percent content of element: -

It contains

% of Carbon = 66 %

% of hydrogen = 13 %

% of oxygen = 21 %

5) Melting point = 262 0c

6) Therapeutic use: - Some studies were carried out in order to explore the

Anticancer, Antiviral, anticoagulants agent and fluorescent brighteners.

7) Industrial applications: - Its derivatives can be used as enhanced antitumor

and other biological activity, and also in dyes building block of synthetic

organic semiconductor & florescent material in LED.


Some naturally occurring coumarin derivatives are umbelliferrone, asculatin, herniarin, imperatorin.

Umbelliferrone Asculatin

(7hydroxy coumarin) (6,7dihydroxy coumarin)

Herniarin Imperatorin

(7methoxy coumarin) (4 phenyl coumarin)

Due to important biological properties & Industrial applications of coumarin & it’s derivatives we wanted to develop a convenient method for

7-methoxy-4-methyl-2-oxo-chromene carbaldehyde.

When we searched the literature we found that Different method available for synthesis of 7-methoxy-4-methyl-2-oxo-chromene carbaldehyde was reported


-:ReportedReported MethodsMethods:-


Reported Methods:-Coumarin Synthesis (7- hydroxy-4-methyl coumarin)

Method I: - Pechmann Condensation reaction

Method II: - Zinc Mediated Coumarin Synthesis


Method III: - Nitration reaction.


-: Retro synthetic Analysis:-


-: OurOur Approach:Approach:-


Our Approach:-Reaction:-

Step I:-

Resorcinol

Step II:-

Step III:-


Mechanism:-

Step I:-


Step II:-


Step III:-


-:-:ExperimentalExperimental work work :-:-


Experiment No :-1

Aim: Preparation of 7-hydroxy- 4-methyl coumarin from resorcinol.

Chemicals:

1) Resorcinol

2) Conc. H2SO4

3) Ethyl aceto acetate

Reaction:-

Procedure:

10 ml. Concentrated sulphuric acid was taken in a conical flask and

cooled in the ice bath. To it a mixture of 1.0 gm of resorcinol and 1.4 ml of

ethyl acetoacetate was added drop wise manner with constant stirring. This

reaction mixture was then kept at room temperature for overnight.

This reaction mixture was then poured on crushed ice and stir vigorously

with the glass rod solid separates out. Filter this yellow solid. Dissolve this solid

in Aq. 10% NaOH and again filter to remove insoluble impurities. Reprecipeted

the solid by adding dil.H2SO4 drop wise to the filtrate and then warming on

water bath.

Filter the crude product, Recrysatalised from ethanol. Dry the product,

take the yield and note down the melting point. Run the TLC in suitable solvent.


Observations:-

Theoretical yield: - Resorcinol = 7-hydroxy-4-methyl coumarin

1 gm = 1.6 gm

Practical yield:-

Practical yield of 7-hydroxy-4-methyl coumarin is = 1.2 gm.

% Practical yield :-

% Practical yield of 7-hydroxy-4-methyl coumarin = 75 %

Melting point :-

Melting point of 7-hydroxy-4-methyl coumarin = 184 oC

TLC:-

Rf value of reactant = 0.92

Rf value of product = 0.71


Solvent used for running TLC is 20 % Ethyl Acetate in Pet Ether.

Result Table:-


Description Compound

Name& structure

Time 12 hr.Theoretical yield 1.6 gmPractical yield 1.2 gm%Practical yield 75%Solvent used EtOHMelting point 1840C

Experiment No :-2

Aim: - Preparation of 4-Methyl 7-Methoxy Coumarin from 4-Methyl 7-

Hydroxy Coumarin.

Chemicals:-

1) 4-methyl 7-hydroxy coumarin

2) Acetone

3) Anhydrous K2CO3

4) DMS

5) 10% Na2CO3

6) Sodium sulphate

Reaction:-

Procedure:-

A solution of 4-methyl 7-hydroxy coumarin (0.5gm) in dry

acetone (15 ml) was treated with anhydrous K2CO3 (1.5 gm) and DMS (1.25 ml)

is added in three portions. The above mixture was stirred and refluxed for 8

hour. After completion of reaction (TLC) the reaction mixture was then filtered

and the residue is washed with hot acetone. The excess of acetone was

recovered by distillation. The remaining methylated compound is extracted with


ether, washed well with 10% Na2CO3 and then with water. The ether layer

dried over sodium sulphate and evaporation of ether gave the product.

Observations:-

Theoretical yield:-

7-hydroxy-4-methyl coumarin = 7-methoxy -4-methyl coumarin

176gm = 190gm

0.5gm = 0.53gm

Practical yield:-

Practical yield of 6-nitro 7- hydroxy-4-methyl coumarin is = 0.392 gm

% Practical yield:-

% Practical yield of 6-nitro 7 -hydroxy-4-methyl coumarin = 73.96%

Melting point:-

Melting point of 6-nitro 7-hydroxy-4-methyl coumarin = 1600C


TLC :-

Result Table:-

Experiment No :-3



Name & structure

Time 8 hr.Theoretical yield 0.53 gmPractical yield 0.39 gm%Practical yield 73.96%Solvent used EtOHMelting point 160 0C

Aim: - Preparation of 4-methyl-7-methoxy, 6-formyl coumarin from 4-methyl-

7-methoxy coumarin.

Chemicals:-

1) N-N dimethyl form amide

2) POCl3

3) 4-Methyl- 7-methoxy coumarin

4) Sodium acetate

Reaction:-

Procedure :-

Measure 0.4 ml of N-N dimethyl form amide in a hard glass test tube and

cool it in ice bath. To this add constant shaking 0.4 ml of POCl3. After

formation of complex is complete, add 0.5 gm of 4-methyl 7-methoxy coumarin

in one portion, put a plastic cover on test tube and for 2 hours. Take care that

moist does not enter into test tube. Pour reaction mixture over 7.5ml saturated

ice cold solution of sodium acetate and keep it aside for 30 min. Filter the

product is obtained , recrystallise by ethanol. Record M.P and TLC.

Observation:-


Theoretical yield:-

7-methoxy 4-methyl coumarin = 6-formyl 7-methoxy 4-methyl coumarin

190gm = 219gm

0.5gm = 0.57gm

Practical yield:-

Practical yield 4-methyl-7-methoxy-6-formyl coumarin of product = 0.328gm

% Practical yield:-

%Practical yield 4-methyl-7-methoxy, 6-formyl coumarin of product=56.14%

Melting point:-

Melting point of methyl-7-methoxy, 6-formyl coumarin = 262 oC

TLC :-


Result Table:-


Name & structure

7-methoxy-4-methyl-2-oxo-2H-chromene-6-carbaldehyde

Time 2 hr.Theoretical yield 0.57 gmPractical yield 0.32 gm%Practical yield 56.14%Solvent used EtOHMelting point 262 0C


-: Spectral data :-



Conclusion and Result :- To conclude, Coumarin showing anti-bacterial properties, anti-

coagulant properties, and coumarin is widespread naturally occurring aromatic heterocyclic compound. The Coumarin (7-Hydroxy 4-metyl) synthesis by Pechmann condensation method is efficient method giving high yield about 75%, which on methylation by using with DMF,K2CO3 and dry acetone resulted with improved yield of 73% gives product 7-Methoxy 4-Methyl Coumarin as major product, this product is confirmed by T.L.C. and physical method technique.

The coumarin (4-methyl-7-hydroxy coumarin)is showing property of fluorescence,hence it is used fluorescent marker. I have synthesized coumarin formylation by various method but coumarin formylation by the approached way proved to be better and efficient method gives high yield about 56.14%.Therefore synthesized 4-methyl 7-methoxy-2-oxo-2H-chromene carbaldehyde is major product, The completion of reaction is confirmed by T.L.C. physical constant and IR spectral analysis data. Spectral data of compound showing following peaks 1745 cm-1 showing presence of lactone ring ,1720 cm-1 showing presence of aldehyde group, 1450-1600 cm-1 showing c=c (unsaturation) aromatic ring,

From above we conclusion that, we developed a convenient, simple, efficient and eco-friendly procedure for the synthesis of 4-methyl 7-methoxy-2-oxo-2H-chromene carbaldehyde.


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Gaikwad 16042012