MICROWAVE ASSISTED GREEN SYNTHESIS OF PHARMACEUTICALLY IMPORTANT DIHYDROPYRIMIDINONES IN FRUIT JUICE MEDIUM
Keywords:
Biginelli reaction, Fruit Juice, Microwave, Dihydropyrimidinone, Green synthesisAbstract
Objective: The objective of this research project was to perform the green synthesis of a series of Dihydropyrimidinone (DHPM) derivatives which are having immense importance in biological and pharmaceutical science, via microwave assisted Biginelli reaction in fruit juice medium.
Methods: Urea and ethyl acetoacetate were made to react with different electron rich as well as electron deficient aromatic aldehydes in various fruit juice medium under microwave irradiation. After successful completion of the reaction the crude product was precipitated out of the reaction medium and after re-crystallization of the crude product the pure desired DHPMs were obtained with quite good percentage of yield.
Results: It was observed that our green Biginelli reaction was completed successfully within few minutes duration and the microwave assisted Biginelli reaction in fruit juice medium was much faster, greener and cleaner compared to that of room temperature Biginelli reaction in the same fruit juice medium. The acidity of the fruit juices and the electronic effect of the aromatic aldehydes have shown significant influence on the rate of reaction.
Conclusion: Thus an efficient, green, cost-effective and eco-friendly method has been developed and reported for the very first time for microwave assisted synthesis of dihydropyrimidinone using some common fruit juices as reaction medium. The fruit juices have served as the solvent cum catalyst in these Biginelli reactions. Our current approach of synthesizing DHPM via microwave assisted Biginelli reaction in fruit juice medium has given a new direction in the field of green chemistry.
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References
Kappe CO. Recent advances in the biginelli dihydropyrimidine synthesis. New tricks from an old dog. Acc Chem Res 2000;33:879−88.
Sakata KI, Someya M, Matsumoto Y, Tauchi H, Kai M, Toyota M, et al. Gimeracil, an inhibitor of dihydropyrimidine dehydrogenase, inhibits the early step in homologous recombination. Cancer Sci 2011;102:1712−6.
Ramesh B, Bhalgat CM. Novel dihydropyrimidines and its pyrazole derivatives: Synthesis and pharmacological screening. Eur J Med Chem 2011;46:1882−91.
Zhu L, Cheng P, Lei N, Yao J, Sheng C, Zhuang C, et al. Synthesis and biological evaluation of novel homocamptothecins conjugating with Dihydropyrimidine derivatives as potent topoisomerase i inhibitors. Arch Pharm Chem Life Sci 2011;344:726−34.
Xuejian QL, Fan M, Xufeng L. Efficient synthesis of dihydropyrimidinones via a three-component Biginelli-type reaction of urea, alkylaldehyde and arylaldehyde. Beilstein J Org Chem 2013;9:2846-51.
Biginelli P. The combination of an aldehyde 1, β-keto ester. Gazz Chim Ital 1893;23:360-416.
Hu EH, Sidler DR, Dolling UH. Unprecedented catalytic three component one-pot condensation reaction: an efficient synthesis of 5-alkoxycarbonyl-4-aryl-3,4-dihydropyrimidin-2(1H)-ones. J Org Chem 1998;63:3454-7.
Lu J, Ma H. Iron(III)-Catalyzed Synthesis of Dihydro pyrimidinones. Improved Conditions for the Biginelli Reaction. Synlett; 2000. p. 63-4.
Ranu BC, Hajra A, Jana U. Indium(III) chloride-catalyzed one-pot synthesis of dihydropyrimidinones by a three-component coupling of 1,3-dicarbonyl compounds, aldehydes, and urea: an improved procedure for the biginelli reaction. J Org Chem 2000;65:6270-2.
Ramalinga K, Vijayalakshmi P, Kaimal TNB. Bismuth(III)-catalyzed synthesis of dihydropyrimidinones: improved protocol conditions for the biginelli reaction. Synlett 2001;6:863-5.
Lu J, Bai Y, Wang Z, Yang B, Ma H. One-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones using lanthanum chloride as a catalyst. Tetrahedron Lett 2000;41:9075-8.
Yadav JS, Reddy BVS, Srinivas R, Venugopal C, Ramalingam T. LiClO4-catalyzed one-pot synthesis of dihydropyrimidinones: an improved protocol for Biginelli reaction. Synthesis 2001;9:1341-5.
Kumar KA, Kasthuraiah M, Reddy CS, Reddy CD. Mn(OAc)3•2H2O-mediated three-component, one-pot,condensation reaction: an efficient synthesis of 4-aryl-substituted 3,4-dihydropyrimidin-2-ones. Tetrahedron Lett 2001;42:7873-5.
Yadav JS, Reddy BVS, Reddy KB, Raj KS, Prasad AR. Ultrasound-accelerated synthesis of 3, 4-dihydropyrimidin-2 (1 H)-ones with ceric ammonium nitrate. J Chem Soc Perkin Trans 2001;1:1939-41.
Ranu BC, Hajra A, Dey SS. A practical and green approach towards synthesis of dihydropyrimidinones without any solvent or catalyst. Org Process Res Dev 2002;6:817-8.
Pramanik T, Wani TA, Singh A. Influence of electronic factors on Solvent-Free and catalyst free Biginelli Reactionâ€. Orient J Chem 2013;29:1209-12.
Pramanik T, Pathan AH. Exploring the utility of fruit juices as green medium for biginelli reaction. Res J Pharm Biol Chem Sci 2014;5:444-9.
Pramanik T, Pathan AH, Gupta R, Singh J, Singh S. Dihydropyrimidinone derivatives: green synthesis and effect of electronic factor on their antimicrobial properties. Res J Pharm Biol Chem Sci 2015;6:1152-7.
Ravichandran S, Karthikeyan E. Microwave synthesis-a potential tool for green chemistry. Int J ChemTech Res 2011;3:466-70.
Mingoes D. The energy efficiency of microwave (MW) irradiation and the ability of MW irradiation to speed up the chemical reaction. Chem Indian 1994;4:596-9.
Choudhary VR, Tillu VH, Narkhede VS, Borate HB, Wakharkar RD. Microwave assisted solvent-free synthesis of dihydropyrimidinones by Biginelli reaction over Si-MCM-41 supported FeCl3 catalyst. Catal Commun 2003;4:449-53.
Misra AK, Agnihotri G, Madhusudan SK. Microwave induced eco-friendly solvent-free Biginelli reaction catalyzed by calcium chloride. Indian J Chem 2004;43B:2018-20.
Sharma S, Mishra S, Gupta M, Mishra A. Microwave assisted one pot synthesis, Mass spectral analysis and DFT studies of 6-Substituted-3,4-dihydro-4-phenylpyrimidin-2(1H)-one. J Mater Environ Sci 2014;5:1079-84.
Bose AK, Pednekar SN, Ganguly S, Chakraborty GM, Manhas S. A simplified green chemistry approach to the Biginelli reaction using ‘Grindstone Chemistry’. Tetrahedron Lett 2004;45:8351-3.
Baskaran SS, Koenig B. Efficient synthesis of 3,4-dihydropyrimidin-2-ones in low melting tartaric acid–urea mixtures. Green Chem 2011;13:1009-13.
Fu NY, Yuan YF, Zhong C, Wang S, Wang, T, Peppe C. Indium (III) bromide-catalyzed preparation of dihydropyrimidinones: improved protocol conditions for the Biginelli reaction. Tetrahedron 2002;58:4801-7.