CH 3204 Semester Project Presentation

Synthesis of a Coumarin derivative using Solvent-free Green

Chemistry approach

Participants:Harsh Vardhan Dwivedi

Roll No: 10MS23, Department of Earth SciencesSandipan Dasgupta

Roll No: 10MS12, Department of Biological Sciences

Indian Institute of Science Education & Research (IISER) Kolkata

Coumarin(IUPAC: 2H-chromen-2-one)

Natural product found in many plants.

Belongs to “Benzopyrone” Class. “Dicoumarol”- produced from

dimerization of 4-hydroxycoumarion is widely used as a anti-coagulant, beacause of its Vitamin-K antagonistic properties.

Coumarin, along with other benzopyrones are widely used a macrophage stimulant to cause regression of local edema.

Shown to have apetite reducing properties, hence widely found among the grazable plants.

Medicinal properties: anti-HIV, anti-tumor, anti-hypertension, anti-arrhythmia, anti-inflammatory, anti-osteoporosis, antiseptic and analgesic, also widely used in treatment of asthma, and lymphedema

Synthesis and Metabolism

General Laboratory Preparation:

PERKIN REACTION :Condensation between salicaldehyde and acetic anhydride to form cinnamic acid followed by intramolecular cyclization to form coumarin, in presence of corresponding alkali salt.

PECHMANN REACTION: Condensation between activated phenols (resorcinol) and carboxylic acid derivatives (ethyl acetoacetate), under acidic conditions.

Metabolism:

The biosynthesis of coumarin in plants occurs via glycosylation, hydrolxylation and cyclization of cinnamic acid.

In mammals, the gene UGT18, has glucorinidase activity for many substrates including coumarin.

Reaction Scheme

Salicaldehyde

Diethyl Malonate

3-carboxylic acid ethyl ester of coumarin

Proposed Mechanism

Four major steps:

I. Proton abstraction from DEM by piperidine.

II. Attack of the Nu- formed to the carbonyl group of salicaldehyde.

III. Attack of the Oxygen lp of phenolic group of salicaldehyde to the cabonyl carbon of Ethyl acetoacetate.

IV. Dehydration.

Experimental Outline

I. 4 ml of salicaldedehyde, 5.6 ml of DEM, 400μl of piperidine taken in R.B.

II.Acid Reflux for ~7 hours at 80° C .

III. Cool product, add water and ethyl acetate, product comes in the ethyl acetate layer, dried in Na2SO4.

IV. Purified by Column Chromatography.

RESULT: Product recovered: 8.34 gm

YIELD: 72.6 %

Characterised by: 1 H-NMR, UV-Vis Spectroscopy.

UV-Vis Spectra (In Ethyl Acetate)

UV-Vis Spectra(In DCM)

Expected UV Peaks

At ~220-250 nm, due to π => π* transition of Benzene ring.

At ~ 280-300 nm, due to n => π * transition of keto group.

Since, the whole compound is in conjugation, there must be a peak of this π => π* transition of higher absorbance.

1 H-NMR Spectra

Chemical Shift (δ, ppm)

1

12

2

3

3 21

CH3 of Et

CH2 of Et

7.98.19.44.2 0.4

Conclusions

3 – carboxylic acid ethyl ester of Coumarin is synthezised from salicaldehyde and Diethyl malonate by solvent free Green Chemistry approach with an yield of around ~ 72.6 %.

Acknowledgements & References

Our sincere acknowledgements to:

1. Dr. Debashish Haldar.

2. Mr. Apurba Pramanik.

3. Mr. Bibudha Parasar.

4. Mr. Amal Narayanan

Selected References:

5. Synthesis and evaluation of some innovative coumarin derivatives containing thiazolidin-4-one ring, ramaganesh et al, 2010.

6. Solvent-Free Coumarin Synthesis, Teizo Sugino and Koichi Tanaka, Chemical Letters 2001.

7. J. A. Joule, K. Mills Heterocyclic Chemistry, 4th edition, Blackwell Science, Oxford, UK, 2000.