Coumarin Synthesis

What is Coumarin?

Coumarin or 1-benzopyran-2-one is an aromatic organic chemical compound with the molecular formula C9H6O2. It is a chemical compound in the benzopyrone class of organic compounds (may be considered as a lactone) found in many plants. The molecule can be depicted as a benzene molecule with two adjacent hydrogen atoms replaced by a chain−(CH)=(CH)−(C=O)−O−, forming a second six-membered heterocycle that shares two carbons with the benzene ring. Coumarin is found naturally in numerous plants specifically in high concentrations in the tonka bean.

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Coumarin’s physical properties describe it as a colourless crystalline solid with a sweet odour, almost comparable to the scent of vanilla and a bitter taste. Though the compound has a pleasant odour, animals tend to avoid it because of its bitter taste. Coumarin is commonly found in a lot of plants where it generally aids in the chemical defence against predators. Due to the inhibition of synthesis of vitamin K, a related compound is used as drug warfarin which inhibits the formation of blood clots and deep vein thrombosis.

 

Preparation of Coumarin

Coumarin is a natural volatile active compound found in several plants. Edible plants such as strawberries and cherries also contain some amounts of coumarin. Some other plants where coumarin is found in substantial amounts are Cassia cinnamon, Ceylon cinnamon, deer tongue,  mullein, and in many cherry blossom tree varieties of the genus Prunus. 

At ambient temperatures, it is a white crystal with a melting point of around 340K. Coumarin may be prepared by several name reactions. The Perkin reaction involving salicylaldehyde and acetic anhydride is a popular method for the preparation of coumarin. The Pechmann condensation provides another reaction to form coumarin and its derivatives. 

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The Kostanecki acylation can also be used to produce chromones. The other reactions to form coumarins include Claisen rearrangement, Wittig, Knoevenagel condensations, and Reformatsky reactions.


Coumarin Reactions

As discussed earlier, there are a lot of name reactions that help in the formation/synthesis of coumarin. 

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The above reaction resembles the Perkins Reaction for the synthesis of coumarin. The mentioned reaction involves the condensation of an aldehyde and a carboxylic acid anhydride in the presence of a weak base like the sodium salt of the acid to yield unsaturated carboxylic acids. The reaction was described by Perkin first in 1868 involving the synthesis of coumarin by heating the sodium salt of salicylaldehyde with acetic anhydride. The reaction applies to aromatic aldehydes. It is very useful for the preparation of substituted cinnamic acids.


Coumarin Synthesis Mechanism

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The above picture shows the mechanism involved in the Pechmann Condensation Reaction for the synthesis of coumarin. German chemist Hans von Pechmann was the scientist who discovered this reaction first. From a phenol and a carboxylic acid or ester containing a β-carbonyl group, Pechmann condensation reaction is used to prepare 4-methyl coumarin. 

To form the new ring, the mechanism includes the process of esterification/trans-esterification followed by the attack of the activated carbonyl ortho to the oxygen. The final step involves the process of dehydration.

FAQs (Frequently Asked Questions)

1. What are the Various Uses of Coumarin?

The various uses of coumarin include -

  • Laser Dyes- In blue-green organic dye lasers, coumarin dyes are used as gain media. Some coumarin laser dyes are coumarins 480, 490, 504. Coumarin tetramethyl laser dyes offer a high range of tunability and are also used as a sensitizer in older photovoltaic technologies.

  • Rodenticide Precursor- Coumarin is commonly used in the pharmaceutical industry as a precursor reagent in the production of several synthetic anticoagulant pharmaceuticals. 

  • Medicine- A coumarin called warfarin with the brand name - Coumadin, is a prescription drug used as an anticoagulant to inhibit the formation of blood clots and is a useful therapy for deep vein thrombosis and pulmonary embolism. It is used to prevent blood clot formation from atrial fibrillation, thrombotic stroke, and transient ischemic attacks.

2. What are the Natural Occurrences of Coumarin? Give a Brief Description of the Biological Function of Coumarin.

  • Natural Occurrence- Coumarin occurs in vanilla grass, sweet woodruff, sweet grass, and sweet-clover which are in turn named “sweet” for the sweet (pleasant) smell of the compound. Coumarin may also be found in extracts of Justicia pectoralis. 

  • Biological Function- Coumarin has appetite-suppressing properties which help in discouraging animals from eating plants that contain the extracts of coumarin. Coumarin is commonly found in a lot of plants where it generally aids in the chemical defence against predators. Due to the inhibition of synthesis of vitamin K, a related compound is used as drug warfarin which inhibits the formation of blood clots, pulmonary embolism, and deep vein thrombosis.