INTRODUCTION:

Microwave energy, originally applied for heating foodstuffs by percy Spencer in the 1940s, has found a variety of technical applications in the chemical and related industries since the 1950s, in particular in the food-processing, drying and polymer industries¹. Other applications range for analytical chemistry (microwave digestion, ashing and extraction) to biochemistry (protein hydrolysis, sterilization), pathology (histoprocessing, tissue fixation) and medical treatments (diathermy)². Microwave assisted organic synthesis has as a new “lead” in the organic synthesis. The technique offers clean, simple, efficient, fast and economic for the synthesis of a number of organic molecules such reaction has new tool in the organic synthesis³.

Conventional method of organic synthesis usually requires longer heating time, tedious apparatus setup which result in higher cost of process and the excessive use of solvents or reagents lead to environmental pollution⁴. This technique is considered as important approach toward green chemistry because this technique is more environments friendly and this technology is used in the laboratory and has the potential to have a large impact on the fields of combinatorial chemistry⁵. The microwave reactions were performed using microwave assisted synthesis on microwave, the reactions were worked up extensively to obtain a pure form of product which was isolated using literature work-up procedures⁶. The microwave is also called as green chemistry because it does not produce any hazardous material like gas fumes or heating using external energy source⁷. Microwave uses electromagnetic radiation that passes through material and causes oscillation of molecule which produces heat⁸. Microwave heating produces heat in entire material in the same rate and the same time at a high speed and at a high rate of reaction⁹. Microwave assisted synthesis has become an important tool to the medicinal chemist for rapid organic synthesis¹⁰. Application of microwave technology in organic synthesis has some of the major advantages like spectacular decrease in reaction in reaction time, improved conversions, clean product formation and wide scope for the development of the new reaction conditions¹¹. A microwave is a form of electromagnetic energy that falls at the lower frequency at the end of electromagnetic spectrum¹². Microwave heating is the best process due to the microwave couple directly with the molecule that are present in the mixture, leading to fast rise in temperature, faster reaction and cleaner chemistry¹³. The microwave is also called as green chemistry because it does not produce any hazardous material like gas fumes or heating using external energy source¹⁴. Microwave uses electromagnetic radiation that passes through material and causes oscillation of molecule which produces heat. Microwave heating produces heat in entire material in the same rate and the same time at a high speed and at a high rate of reaction. Microwave assisted synthesis has become an important tool to the medicinal chemist for rapid organic synthesis. Conventional method of organic synthesis usually requires longer heating time, tedious apparatus setup which result in higher cost of process and the excessive use of solvents or reagents lead to environmental pollution¹⁵. Growth of green chemistry holds necessary potential for the reduction of by product, a reduction in the waste production and a lowering of energy costs. Due to its ability to couple directly with reaction molecule and passing thermal conductivity leading to fast rise in the temperature microwave irradiation had used to improve many organic synthesis. The Principle behind the heating in microwave oven is because interaction of charged particle of reaction material with electromagnetic wavelength of particular frequency. The phenomena of the producing heat by electromagnetic irradiation are either by conduction or collision¹⁶.

MATERIAL AND METHODS:

All reagents used were of synthetic grade. Melting point were recorded by open capillary method and are uncorrected. Experimental were performed using microwave synthesizer (catalyst). Comparitively the reactions were performed using conventional methods of synthesis using reflux condenser. The reactions were monitored with silica gel G at specific hours of synthesis. The time for the conventional and microwave assisted synthesis were noted.

Synthesis of Phenacetin¹⁵:

A. Microwave assisted reaction:

Step I: Suspend 2g of p-amino phenol in 6ml distilled water in conical flask. Add 2.2ml acetic anhydride with stirring. Shake the reaction mixture vigorously and warm on a water bath till almost clear solution is firmed. Cool the conical flask in ice bath. Filter the product, wash with cold water and recrystallize from hot water.

Step II: Take clean sodium 0.5g in round bottom flask containing 10ml absolute alcohol. After vigorous reaction has subsided, if sodium is not completely dissolved. Then, warm the flask on water bath till sodium completely dissolved. Cool the reaction mixture and add 3g of p-acetyl amino phenol. Add slowly ethyl iodide (4 g, 2ml) through condenser. Irradiate the mixture in microwave at 340 watt for 5 min. Pour 20ml of water. Cool the round bottom flask in an ice bath. Filter the product, wash with cold water. If solution is coloured, then crude product is dissolved in 20ml rectrified spirit. Add activated charcoal (1g) and filter. Treat the clear solution with hot water and allow cooling. Filter at pump and dry. M.pt: 132-134^◦C.

B. Conventional synthesis:

Approximately 20 min of reflux is required to obtain the product using the equimolar quantities.

Scheme-I

Step I: Synthesis of p-acetyl amino phenol

Scheme-II

Step II: Synthesis of phenacetin

Synthesis of p-acetamidobenzenesulphonyl chloride¹⁹:

A. Microwave assisted reaction:

Carefully add 6gm of dry powered acetanilide, with occasional shaking to 14ml of chlororsulphonic acid in 250ml round Erlenmeyer flask and then irradiate the mixture at 340 watt for 10 min. Cool the mixture and pour it carefully on to about 30gm of crushed ice, sulphonyl chloride seperates as white solid. Filter off the sulphonyl chloride; wash with water and drain. Recrystallize with chloroform. M.pt: 147-149^◦C.

B. Conventional synthesis:

Approximately 30 min of reflux is required to obtain the product using the equimolar quantities.

Scheme-III

Synthesis of benzoic acid²⁰:

A. Microwave assisted reaction:

Take 3gm of benzanilide and 10 ml of sulphuric acid in 250ml of round bottom flask and irradiate the mixture at 225 watt for 10 min. Some of the benzoic acid will vaporize in the stram and solidify in the condenser. Pour 30 ml of hot water down the condenser. This will dislodge and partially dissolve the benzoic acid. Cool the flask in ice water; filter with Buchner funnel and dry it. M.pt: 120-122^◦C.

B. Conventional synthesis:

Approximately 30 min of reflux is required to obtain the product using the equimolar quantities.

Scheme-IV

Synthesis of 2-methyl benzimidazole¹⁸:

A. Microwave assisted reaction:

Place 3 g of o-phenylene diamine, 10ml of water and 3 ml of acetic acid and irradiate the mixture at 225 watt for 10 min. Make the reaction mixture, basic by gradual addition of conc. ammonia solution. Collect the precipitate of product and recrystallize from 10% aqueous ethanol. M.pt: 175-177^◦C.

B. Conventional synthesis:

Approximately 1 hr of reflux is required to obtain the product using the equimolar quantities.

Scheme-V

Synthesis of benzocaine¹⁹:

A. Microwave assisted reaction:

Step I: Take 3gm of p-nitrobenzoic acid, 7ml of absolute ethanol and o.2ml of conc. H2SO4 in round bottom flask. Irradiate the mixture for 15 min. Distill off excess alcohol and allow cooling. Pour the residue into 10ml of water contained in a seperating funnel and rinse the flask with a few ml of water, which are also poured into the separating funnel. Add about 5ml of carbon tetrachloride and shake the mixture vigorously, upon standing, heavy solution of methyl benzoate in CCl₄ seperates sharply and rapidly at the bottom of funnel. Run off the lower layer carefully, reject the upper layer, return the methyl; benzoate to the funnel and shake it with a strong solution of sodium hydrogen carbonate until all free acid is removed and no further evolution of CO₂ occurs. Wash once with water and dry by pouring into a small dry conical flask 2gm of MgSO₄. Stopper the flask, shake for 5 min and allow standing for at least half an hour with occasional shaking. Filter the solution directly to round bottom flask fitted to a still head caring a 360 thermometer and an air condenser. Add a few boiling chips and distill from an air bath. Raise the temperature slowly and heat strongly then collect the crude ethyl p-bitrobenzene.

Step II: In 250ml of round bottom flask, place 2g of ethyl p-nitrobenzoate and 2g of granulated tin. Measure 5ml of conc. HCl, pour about 1ml of this acid to condenser and shake the contents of the flask steadily. The mixture becomes warm and before long the reaction should be quite vigorous, if it boils very vigorously, moderate the reduction by temporsrily immersing the flask in cold water. When the initial slackness of its own pour another 1ml of HCl, Shake the flask steadily to ensure through mixing and cool again if the reaction becomes too violent. Do not cool more than is necessary to keep the reaction under control, keep the mixture well shaken. Proceed in this way until all the 5ml of acid has been added. Irradiate the mixture at 340 watt for 10 min, i.e until the odour of nitrobenzene is no longer perceptible and a few drops of the reaction mixture when diluted with water yield a perfectly clear solution. During the course of the reaction, particularly during cooling, aniline chlorostannate may separate as a white or yellow crystalline complex. Cool the reaction mixture to room temperature and extract and evaporate to dryness. Recrystallize with ethanol. M.pt: 88-90^◦C.

B. Conventional synthesis:

Approximately 1hr of reflux is required to obtain the product using the equimolar quantities.

Scheme-VI

Step I: Synthesis of ethyl p-nitrobenzoate

Scheme-VII

Step II: Synthesis of benzocaine

Synthesis of 3H-quinazolin-4-one²⁰:

A. Microwave assisted reaction:

Take and mix 3g of methyl anthranilate and 7ml of formamide in 250ml of two necked round bottom flask. Then subject to microwave irradiation at 350 watt for 10 min and reaction mixture is allowed to cool at room temperature and then pour on ice water, the solid separate out is filtered by Buchner funnel and recrystallize with methanol. M.pt: 172-174^◦C.

B. Conventional synthesis:

Approximately 45 min of reflux is required to obtain the product using the equimolar quantities.

Scheme-VIII

RESULT AND DISCUSSION:

Table 1 shows comparision of the time taken by microwave assisted synthesis and % yield of compound.

CONCLUSION:

Microwave assisted synthesis is faster, better and safer green chemistry approach for the traditional reactions. The time taken for the synthesis is drastically reduced by the microwave assisted synthesis. Several named reactions were carried out using microwave assisted synthesis, which complied in spectral assignments as that of those with products obtained from the conventional methods.

ACKNOWLEDGEMENT:

I express my sincere thanks to Vice-principal Prof. Dr. S. K. Mohite for providing me all necessary facilities and valuable guidance extended to me.

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Received on 05.05.2020 Modified on 24.05.2020

Asian J. Research Chem. 2020; 13(4):261-264.

DOI: 10.5958/0974-4150.2020.00051.6

Name of the compound	% yield from MWI	Time taken by conventional synthesis in min or hours	Time taken by MWI in minutes
Phenacetin	84.34	20 min	5
p-acetamidobenzenesulphonyl chloride	94.23	1 hr	10
benzoic acid	78.12	30 min	10
2-methyl benzimidazole	87.69	1 hr	15
benzocaine	92.34	1 hr	15
3H-quinazolin-4-one	88.45	45 min	10