7-Hydroxy 4-methyl coumarin synthesis
BP607P Medicinal Chemistry III Practical : I Preparation of drugs Sulphanilamide * 7-Hydroxy, 4-methyl coumarin * Chlorobutanol * Triphenyl imidazole * Tolbutamide * Hexamine II Assay of drugs Isonicotinic acid hydrazide * Chloroquine * Metronidazole * Dapsone * Chlorpheniramine maleate * Benzyl penicillin III Microwave irradiation technique Synthesis of Phenytoin by Microwave * Synthesis of Aspirin by Microwave IV Drawing structures and reactions using chem draw®
Aim: Synthesis and submit Synthesis of 7-Hydroxy-4-methyl coumarin.
Principle:
A general synthesis of coumarins involves the interaction of a phenol with a β- ketoester in presence of an acid condensing agent (Pechmann reaction). Concentrated sulphuric acid is usually used as the condensing agent for simple monohydric phenols and β- ketoesters, although phenol itself reacts better in the presence of aluminium chloride.
The mechanism of the reaction to involve the initial formation of a β- hydroxy ester, which then cyclise and dehydrates to yield the coumarin. Polyhydric phenols, particularly here the two hydroxy groups are meta oriented, react with great ease and sulphuric acid is used as the condensing agent with careful temperature control to ensure a good yield.
Reaction
Chemicals Requirements:
Conc. Sulphuric acid-7.5 ml Ice – q.s
Resorcinol – 1.2 g Sodium Hydroxide- q.s
Ethylacetoacetate – 2.4 ml Ethanol – q.s
Procedure
Take 1 litre of concentrated sulphuric acid in a 3 litres capasity 3 necked flask fitted with a thermometer, mechanical stirrer and a dropping funnel. Immerse the flask in an ice bath. When the temperature falls below 10 C, add a solution of 100 g (0.91 mol) of resocinol in 134 g (130.5 ml, 1.03 mol) of redistilled ethyl acetoacetate drop wise and with stirring.
Maintain the temperature below 10 C by means of an ice-bath during the addition (2h). Keep the mixture at room temperature for 18 hr and then pour it into a mixture of 2 kg of crushed ice with vigours stirring and add 3 litter of water.
Collect the precipitate by suction filteration and wash it with three 25 ml portion of cold water. Dissolve the solid in 1500 ml of 5 percent sodium hydroxide solution, filter and add dilute 2 M sulphuric acid (about 550 ml) with vigourous stirring until the solution is acid to litmus.
Filter the crude 4-methyl-7-hydroxy coumarin at the pump, wash with four 25 ml portions of cold water and dry at 1000C. The yield is 155g (97%).
Recrystallise from 95 percent ethanol: the pure compound separete in colourless needles, m.p. 185 C.
Use
Laser dye.
Starting material for production of the insecticide ‘ hymecromone’.
Report:
7- hydroxy -4- methyl coumarin was synthesized and the percentage yield was found to be …….. %.
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