A Comparative Study of Conventional and Microwave Assisted Synthesis of Basic Heterocyclic Rings at Undergraduate Level

 

Vijaya Vichare*, Ashwini Sawant, Indira Gaud, Leena Patil and Vrushali Tambe.

P. E. S’s, Modern College of Pharmacy (for Ladies), Borhadewadi, Dehu-Alandi Road, Moshi, Pune-412105.

*Corresponding Author E-mail: mane_vijaya@yahoo.com

ABSTRACT:

In general the pharmacologically active compounds are mostly heterocyclic in nature. The heterocyclic compounds shows different pharmacological activities such as Analgesic, Anti-inflammatory, Antipyretic, Anti-bacterial, Antifungal, Anti allergic, Insecticide, Herbicide etc. Now a day’s Microwaves are commonly used for synthesis organic compounds due to its beneficts like Reaction rate acceleration, milder reaction condition, higher chemical yield, lower energy usage, different reaction selectivities, design versatilies for wide range of application.

Therefore an attempt has been made to syntheisze some basic heterocyclic rings by using microwave energy. We have synthesized some basic heterocyclic rings like 2,3-Diphenylquinoxaline, 3-Methyl-1-phenyl pyrazole-5-one,  5,5-Diphenyl hydantoin, Benzimidazole, 2-Methylbenzimidazole, 2-Phenylbenzimidazole and 1,2,3,4-Tetrahydrocarbazole conventionally as well as by using microwave energy.

The completion of reaction was checked by TLC and purity of compounds was checked by melting point. Time required for the reaction and chemical yield were compared by both methods. It was observed that the compounds can be synthesized successfully by microwave method where time is reduced by 5-15 times and chemical yield is increased by 5-13%.

 

 

 

INTRODUCTION:

Microwave-assisted synthesis has evolved as a highly versatile, revolutionary technique that allows more rapid, efficient synthesis and screening of chemical substances to identify compounds in lead compound optimization¹. It has received considerable attention over the years due to the eminent advantages like shorter reaction times (typically from days or hours to minutes or seconds), higher yields, high purity of resulting products, simple reaction conditions, faster optimization of reaction conditions, low cost, simplicity in processing and handling and feasibility^2-5. Solvent-free reaction leads to a clean, eco-friendly and economic technology. Reactions on solid support without using solvent usually with open vessel in domestic microwave ovens are currently in use for synthetic chemist to create eco-friendly atmosphere.^6,7.

 

It has been applied successfully in various fields of synthetic organic chemistry⁸, including cycloaddition reactions⁹, heterocycle synthesis¹⁰, the rapid preparation of radio labeled materials¹¹ , transition metal catalyzed processes, solvent free reactions³, and phase transfer catalysis¹². In fact, it is becoming evident that microwave approaches can be developed for most chemical transformations requiring heat.

 

The heterocyclic compounds show different pharmacological activities such as Analgesic, Anti-inflammatory, Antipyretic¹³, Antimicrobial¹⁴, Anti allergic¹⁵, Anthelmintic¹⁶ etc.

Therefore an attempt has been made to syntheisze some basic heterocyclic rings by using microwave energy.

 

MATERIALS AND METHODS:

Chemicals were purchased from S. D. Fine Chem. Ltd., (Mumbai) and were used without any further purification. All the reactions were carried out in CATALYST Scientific Microwave Synthesis System. The progress of the reaction was monitored on percolated silica gel 60 F254 plates (Merck) and spots were visualized by exposure to iodine vapors or under ultra violet light. Melting points were determined by open capillary tube method Veego VMP-1 Apparatus and expressed in ° C and are uncorrected.

EXPERIMENTAL:

Synthesis of selected compounds was carried out by conventional as well as microwave method. The time required for completion of synthesis and yields were studied and compared by both the methods.

 

Conventional method^17,18:

I.       Synthesis of 2,3-Diphenylquinoxaline:

To a warm solution of Benzil (2.1g , 0.01mol) in 8 ml of rectified spirit added a solution of o-phenylenediamine (1.1g , 0.01 mol) in 8 ml of spirit. Heated on water bath for 30 min. Added water  till cloudiness persists. Allowed to cool, filtered and recrystallised using aq. ethanol.

 

II.     3-Methyl-1-phenyl pyrazole-5-one:

A mixture of ethylacetoacetate (4.9 ml, 0.038 mol) and phenylhydrazine (3.65 ml, 0.037 mol) was heated together on a boiling water bath for 2 hrs in a fume cupboard, with occasional stirring. The heavy reddish syrup was allowed to cool. To this syrup, was added 100 ml of solvent ether and the mixture was stirred vigorously. The syrup, insoluble in ether, got solidified, which was filtered and washed thoroughly with solvent ether to remove coloured impurities.  The crude product, thus obtained, was recrystallised from 50 % ethanol-water.

 

III.   5,5-Diphenyl hydantoin:

A mixture of (Benzil 5.3 g, 0.025 mol), urea (3.0 g (0.05 mol), 15 ml of 30%  Sodium hydroxide solution and 75 ml of ethanol was refluxed for 2 hrs. Colled to room temperature and poured in 125 ml water, made strongly acidic with Conc. Hydrochloric acid. Cooled in ice-water, filtred, recrystallised using spirit.

 

IV.   Benzimidazole:

O-Phenylenediamine (2.7 g, 0.25 mol) and 90 % formic acid (1.6 ml, 0.34 mol) were refluxed in  a round bottom flask on a water bath for 2 hours. The reaction mixture was cooled and alkalinized with 10 % sodium hydroxide solution. It was then filtered off to get crude benzimidazole. The residue was washed with ice-cold water and recrystallised with boiling water using decolourising carbon.

 

V.     2-Methylbenzimidazole:

A mixture of o-phenylenediamine (3.24 g, 0.03 mol) and acetic acid (5.4 g, 0.09 mol) was heated together under reflux for 45 minutes. The reaction mixture was cooled and distinctly basified by gradual addition of concentrated ammonia solution. The precipitate was filtered, washed with water and recrystallised from 10 % aqueous ethanol.

 

VI.   2-Phenylbenzimidazole:

A mixture of o-phenylenediamine (3.24 g, 0.03 mol) and  phenylacetic acid (12.3 g, 0.09 mol) was heated together under reflux for 45 minutes. The reaction mixture was cooled and distinctly basified by gradual addition of concentrated ammonia solution. The precipitate was filtered, washed with water and recrystallised from 40 % aqueous ethanol.

 

VII. 1,2,3,4-Tetrahydro Carbazole:

A mixture of Cyclohexanone (4.9 g, 0.05 mol) and 18 gm glacial acetic acid heated under reflux with stirring and adding redistilled pheny hydrazine (5.4 g, 0.05 mol) during 1 hr. Stirring was continued for furhter 1 hr. Reaction mixture was poured in a beaker , stirred vigorously, cooled, filtred and recrystallised with methanol.

 

Microwave method:

Same ammounts of chemicals were used for all above synthesis, but heating was done by microwave irradiation at different levels and completion of reaction was checked by TLC.

 

RESULTS AND DISCUSSION:

All the compounds were synthesized successfully by using microwave irradiation. The compounds obtained in higher yeilds and reduced reaction time by microwave method than conventional method (Table 1). Decrease in heating time reduced cost of electricity and environmental pollution.

 

 

Table 1:Yields and Reaction time of compounds by Conventional and Microwave method

Sr. NO.	COMPOUND	CONVENTIONAL METHOD		MICROWAVE  METHOD
		YIELD (% w/w)	TIME (min)	YIELD (% w/w)	TIME (min)	LEVEL/ POWER
1	Benzimidazole	70	120	82	10	Level-5: 350 watt
2	2-Methylbenzimidazole	50	45	55	10	Level-5: 350watt
3	2-Benzylbenzimidazole	50	45	58	10	Level-5: 350 watt
4	2,3-Diphenylquinoxaline	50	30	61	5	Level 3: 245 watt
5	3-Methyl-1-phenylpyrazole-5-one	72	120	85	5	Level 3: 245 watt
6	5,5-Diphenyl hydantoin	36	120	46	5	Level 3: 245 watt
7	1,2,3,4-Tetrahydrocarbazole	57	60	65	6	Level-5: 350watt

 

 

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Received on 15.05.2011        Modified on 25.07.2011

Accepted on 14.08.2011        © AJRC All right reserved