Comparative Study of Conventional and Microwave Assisted Synthesis of some Organic Reactions

 

Akshay R. Yadav*, Shrinivas K. Mohite, Chandrakant S. Magdum

Department of Pharmaceutical Chemistry, Rajarambapu College of Pharmacy,

Kasegaon, Maharashtra, India-415404.

*Corresponding Author E-mail: akshayyadav24197@gmail.com

 

ABSTRACT:

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 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 pollution. 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 chemistry. 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 procedures. The products were further recrystallized with suitable solvents. The reactions were monitored with TLC intermittently for microwave assisted synthesis and hourly for conventional method of synthesis.

 

KEYWORDS: Conventional method, green chemistry, combinatorial chemistry, microwave reactions.

 

 

 

INTRODUCTION:

Traditionally, organic synthesis is carried out by conductive heating with an external heat source. This is a comparatively slow and inefficient method for transferring energy into the system, since it depends on the thermal conductivity of the various materials that must be penetrated, and results in the temperature of the reaction vessel being higher than that of the reaction mixture1. Microwave-enhanced chemistry is based on the efficient heating of materials by “microwave dielectric heating” effects2. This phenomenon is dependent on the ability of a specific material to absorb microwave energy and convert it into heat3.

 

Microwave is defined electromagnetic waves with vacuum wavelength ranging between 0.1 to 100cm or, equivalently, with frequencies between 0.3 to 300GHz. With microwave heating, the energy can be applied directly to the sample rather than conductively, via the vessel4. Heating can be started or stopped instantly, or the power level can be adjusted to match the required5. A microwave is a form of electromagnetic energy that falls at the lower frequency at the end of electromagnetic spectrum6. 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 chemistry7. The microwave is also called as green chemistry because it does not produce any hazardous material like gas fumes or heating using external energy source8. 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 synthesis9. 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 conditions10. Microwave heating depends upon two major factors first is the pre-exponential factor ‘A’ which describe the molecular mobility and depends upon the frequency of vibrations of the molecule at reaction interface11. The other reason is the alteration in the exponential factors by affecting the free energy of activation. With microwave heating heat is directly applied to the sample not to the vessel or container that’s why it icreases the rate of reaction very quickly12. We know that with every 10 rise in temperature the rate of reaction become double i.e. if for a reaction to be completed it takes 80 min in conventional system but if the same reaction takes place in microwave irradiation it will takes only 10 min this shows that in microwave irradiation the rate of reaction or synthesis and the reaction speeds up13-14.

 

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 2-acetoxy benzoic acid15:

A.    Microwave assisted reaction:

Slowly mix 9ml of acetic anhydride with 5g of salicyclic acid in 250ml Erlenmeyer flask. Carefully add 5 to 10 drops of 85% phosphoric acid to the solution an mix thoroughly. Irradiate the mixture under microwave, 225 watt for 5 min till all salicyclic acid dissolve. After completion of the reaction, caustiously add 10ml of distilled water to the mixture, and the cool solution on an ice bath until aspirin crystallize. Filter the crystals by using a Buchner filter and extract by using chilled water. M.pt: 134-136◦C.

 

B.    Conventional synthesis:

Approximately 15 min of reflux is required to obtain the product using the equimolar quantities.

 

Scheme-I

Synthesis of benzilic acid16:

A.    Microwave assisted reaction:

Step I: Synthesis of potassium salt of benzilic acid:

Place a solution of 2g of potassium hydroxide in 4ml water in round bottom flask, and then add 4ml of rectified spirit and 2gm of benzil. A deep bluish-black solution is produced. Irradiate the mixture under microwave, 340 watt for 6 min. Pour the contents of the flask into porecelain dish and cool in ice. The potassium salt of benzilic acid crystallizes out. Filter off the crystals and wash with a ice- cold alcohol.

 

Step II: Synthesis of benzilic acid:

Dissolve potassium salt in about 15ml of water and add slowly with stirring two or three drops of conc. HCl. The ppt thus produced is red-brown in colour and is somewhat sticky. Filter this off; the filterate should be nearly colourless. Continue the addition of hydrochloric acid with stirring until the solution is acid to congo red paper. Filter off the product, wash it thoroughly with cold water and allow it to dry. Recrystallize from hot benzene or from hot water. M.pt: 150-152◦C.

 

B.    Conventional synthesis:

Approximately 15 min of reflux is required to obtain the product using the equimolar quantities.

 

Scheme-II

 

Synthesis of Benzophenone oxime17:

A.    Microwave assisted reaction:

Take a mixture of 3gm of benzophenone, 2gm of hydroxylamine hydrochloride, 6 ml of rectified spirit and 2ml of water in 250ml of round bottom flask. Add 3gm of NaOH in portions with shaking. If reactions becomes too vigorous; cool the flask by holding it under running tap water. When all the sodium hydroxide has been added, irradiate the mixture under microwave, 340 watt for 3 min. Cool and pour the contents of the flask into solution of 9 ml of conc. HCl in 250ml of water in a beaker. Filter the ppt, wash thoroughly with cold water and dry in a oven at 40◦C. M.pt: 208-209◦C.

 

B.    Conventional synthesis:

Approximately 10 min of reflux is required to obtain the product using the equimolar quantities.

 

Scheme-III

 

Synthesis of P-amino benzoic acid17:

 

A.    Microwave assisted reaction:

Place 3g of p-nitrobenzoic acid in a 250m l round bottom flask and introduce 4 gm powered tin and 8ml conc. HCl. Irradiate the mixture under microwave, 225 watt for 3 min. Shake the flask frequently; occasional gentle warming may be necessary. After about 5 min, most of the tin will have reacted and a clear solution remains. Allow to cool and add conc. ammonia solution until the solution is just alkaline to litmus. Filter off solid with Buchner funnel ad allow the product to dry. M.pt: 185-187◦C.

 

B.    Conventional synthesis:

Approximately 10 min of reflux is required to obtain the product using the equimolar quantities.

 

Scheme-IV

 

Synthesis of Sulphanilamide18:

A.    Microwave assisted reaction:

Place 5g of p-acetamidobenzenesulphonamide; add 3ml of Conc. HCl and 10ml of water. Irradiate the mixture under microwave, 225 watt for 10 min. Cool the solution to room temperature. Heat further for short period if solid seperates. Treat the solution with declourizing carbon. Filter the hot solution. Collect the filterate in a beaker and caustiously add 4g of solid sodium hydrogen carbonate in portion with stirring. After evolution of gas, test suspension with litmus paper. If still acid, add little sodium hydrogen carbonate till neutral. Cool in ice, filter with Buchner funnel. M.pt:163-165◦C.

 

B.    Conventional synthesis:

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

 

Scheme-V

 

RESULT AND DISCUSSION:

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

 

Table 1: Comparision of the time taken by Microwave irradiation and time taken by conventional synthesis.

Name of the compound

% yield from

MWI

Time taken by conventional synthesis in min hours

Time taken by MWI in minutes

2-acetoxy benzoic acid

92

15

5

benzilic acid

80

15

6

Benzophenone oxime

86

10

3

P-amino benzoic acid

94

10

5

Sulphanilamide

78

45

10

 

CONCLUSION:

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 synthesis. The time taken for the synthesis is drastically reduced by the microwave assisted synthesis. Important advantage of this technology includes highly accelerated rate of the reaction time with an improvement in yield and quality of product. 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 chemistry, screening, medicinal chemistry and drug development.

 

REFERENCES:

1.     Surati M, Jauhari S, Desai K, A Brief Review: Microwave assisted organic reaction. Arch. Appl. Sci. Res., 2012, 4(1):645-661.

2.     Yadav A, Mohite S, Magdum C, Synthesis, Characterization and Biological Evaluation of Some Novel 1,3,4-Oxadiazole Derivatives as Potential Anticancer Agents, Int J Sci Res Sci Technol. March-April-2020; 7 (2): 275-282.

3.     A K Nagariya, A K Meena, A K Yadav, U S Niranjan, A K Pathak, B Singh, M M Rao, Microwave assisted organic reaction as new tool in organic synthesis. J Pharm. Res. 2010, 3(3), 575-580.

 

4.     Gaba M, Dhingra N, Microwave Chemistry: General features and Applications. Ind J Pharm Edu Res, 2011, 45(2): 175-183.

5.     Gedye R, Smith F, Westaway K, The use of microwave ovens for rapid organic synthesis. Tetrahedron Lett. 1986; 27: 279-282.

6.     Rajak H, Mishra P. Microwave assisted combinatorial chemistry: The potential approach for acceleration of drug discovery. J Sci Indus Res. 2004; 63:641-654.

7.     Langa F, Cruz P, Hoz A, Ortiz A, Barra E. Microwave irradiation: more than just a method for accelerating reactions. Comtemp Org Synth. 1997; 4: 373-386.

8.     Yadav A, Mohite S, Design, Synthesis and Characterization of Some Novel benzamide derivatives and it’s Pharmacological Screening. 2020. Int J Sci Res Sci Technol. 7(2): 68-74.

9.     Gupta M, Paul S, Gupta R. General characteristics and applications of microwave in organic synthesis. Acta Chim Slov 2009; 56: 749-764.

10.  Rajput M. D, Yadav A. R, Mohite S.K, Synthesis, Characterization of Benzimidazole Derivatives as Potent Antimicrobial Agents. 2020. Int. J. Pharm. 17(4): 279-285.

11.  Joshi U J, Gokhale K M, Kantikar A P, Green chemistry: need for the hour, Ind. J. Edu. Res. 2011; 168-174.

12.  Gasgnier M, Loupy A, Petit A, Jullien H, New developments in the field of energy transfer by means of monomade microwaves for various oxides and hydroxides. J. Alloys Comp. 1994; 204: 165-72.

13.  Elander N, Jones JR, Lu SY, Stone-Elander S. Microwave-enhanced radiochemistry. Chem Soc Rev 2000; 29;239-249.

14.  A. Tiwari, R. Kumar, A practical book of pharmaceutical medicinal chemistry. Nirali prakashan:38

15.  Furniss B. S, Hanford A. J., Vogel’s textbook of practical chemistry, 5ed. Pearson education: 1989. P.1046-1047.

16.  Gavarkar P. S, C. S. Magdum, S. K. Mohite, R. S. Adnaik, Practical’s in Medicinal Chemistry, 1ed. Unicorn publication: 47-82.

17.  Jain K, Miniyar P, Nargud L, A Practical Book of Pharmaceutical Organic Chemistry, 1ed. Nirali Prakashan: 5.20-5.21.

 

 

 

Received on 08.04.2020          Modified on 30.04.2020

Accepted on 21.05.2020   ©Asian Pharma Press All Right Reserved

Asian J. Pharm. Res. 2020; 10(3):217-220.

DOI: 10.5958/2231-5691.2020.00037.4