Green chemistry aspect is the chemical approach that has been studied in the past two decade. One of the principles is the development of green synthesis process that is friendly for the environment. This research showed that papain can be used as catalyst for Knoevenagel reaction with 3 kinds of substituted-benzaldehyde and malononitrile as substrates in aqueous medium. The best reaction condition with 80% yield was reached by utilizing of 25 mg papain/mmol substrate. Reaction was conducted at ambient temperature and pressure for 30 min. Products were as yellowish to yellow needle crystals and successfully characterized by melting point, UV-Vis, IR, mass spectra, and 13C & 1H-NMR, named as 2-(4-hydroxybenzylidene)-malononitrile); 2-(3-hydroxybenzylidene)-malononitrile); and 2-(4-hydroxy-3-methoxybenzylidene)-malononitrile).

Bahasa Abstract

Aspek green chemistry merupakan pendekatan kimia yang banyak digunakan dalam dua dekade belakangan ini. Salah satu prinsipnya adalah pengembangan metode sintesis yang lebih “hijau”. Hasil penelitian ini menunjukkan bahwa papain terbukti dapat mengkatalisis reaksi Knoevenagel untuk 3 macam senyawa benzaldehida tersubstitusi dan malononitrile yang dilangsungkan dalam pelarut air. Kondisi terbaik, dengan rendemen sekitar 80%, diperoleh pada penggunaan papain sebanyak 25 mg/mmol substrat. Reaksi dilangsungkan pada suhu dan tekanan ruang selama 30 menit. Tiga produk yang diperoleh berbentuk kristal jarum berwarna kekuningan hingga kuning dan telah berhasil dikarakterisasi, melalui penentuan titik leleh, spektrum UV-Vis, IR, Massa, serta 13C dan 1H-NMR, sebagai senyawa 2-(4-hydroxybenzylidene)-malononitrile); 2-(3-hydroxybenzylidene)-malononitrile); dan 2-(4-hydroxy-3-methoxybenzylidene)-malononitrile).


Amri, E., & Mamboya, F. (2012). Papain, a aplant enzyme of biological importance: a review. American Journal of Biochemistry and Biotechnology, 8(2),99-104

Anatas, P. T., & Warner, J. C. (1998). Green chemistry: Theory and practice. Oxford: Oxford University Press

Azarkan, M., Moussasaoni, A. E., van Wuytswinkel, D., Dehon, G., Looze, Y. (2003). Fractionation and purification of the enzyme stored in the latex of Carica papaya. J. Chromatogr. B., 790, pp-229- 238.

Bang, H. X., Zhi, G., Yan, H. H. (2012). Biocatalytic Knoevenagel reaction using alkaline protease from Bacillus licheniformis. Biocatalysis and Biotransformation, 30 (2), pp. 238-244.

Bhuiyan, M. M. H., Hossain, M. I., Alam, A., Mahmud, M. M. (2012) Microwave assisted Knoevenagel condensation: synthesis and antimicrobial activities of some arylidine-malononitrile. Chemistry Journal, vol. 02, issue 01, pp. 31-37.

Constantin, M-A., Conrad, J., Beifuss, U. (2012). Laccase-catalyzed oxidative phenolic coupling of vanillidene derivatives. Green Chemistry, 14, pp. 2375-2379.

Deb, M. L. & Bhuyan, P. J. (2005). Uncatalysed Knoevenagel condensation in aqueous medium at room temperature. Tetrahedron Letters, 46, pp. 6453-6456.

Gou, W. L., Jia, X., Wen, Q. Z. (2013). Highly efficient Knoevenagel condensation reactionsby a proline-functionalized polyacrylonitrile fiber. Chinese Chemical Letters, 24, pp. 52-54.

Hosseini-Sarvari, M., Sharghi, H., Etemad, S. (2007). Solvent free Knoevenagel condensations over TiO 2 . Chinese Journal of Chemistry, 25, pp. 1563-1567.

Jiang, L., Yu, H. (2014). Enzymatic promiscuity: Eschericia coli BioH esterase-catalysed Aldol reaction and Knoevenagel reaction. Chem. Res. Chin. Univ., 30 (2), pp. 289-292.

Li, J. J., Johnson, D. S., Sliskovic, D. R., Roth, B. D. (2004). Contemporary drug synthesis, Wiley-Interscience. New Jersey, USA.

Linthorst, J. A. (2010). An Overview: Origins and Development of Green Chemitry. Found Chem, 12, pp. 55-68.

Madivada, L. R., Anumala, R. R, Gilla, G., Alla, S., Charagondla, K., Kagga, M., Bhattacharya, A. & Bandichhor, R. (2009). An Improved Process for Pioglitazone and Its Pharmaceutically Aceptable Salt. Organic Process Research & Development,Vol.13, No.6, pp. 1190-1194.

Martinez, C. A., Hu, S., Dumond, Y., Tao, J., Kelleher, P. & Tully, L. (2008). Development of a Chemoenzymatic Manufacturing Process for Pregabalin. Organic Process Research & Development, Vol.12, No.3, pp. 392-398.

Pal, R. (2014). Visible light induced Knoevenagel condensation: a clean and efficient protocol using aqueous fruit extract of Tamarindus indica as catalyst. International Journal of Advanced Chemistry, 2 (1), pp. 27-33.

Ricardo, M. (2012). Green Chemistry – Aspects for the Knoevenagel reaction, green chemistry – environmentally benign approaches, Dr. Mazaahir Kidwai (Ed.), ISBN: 978-953-51- 0334-9, InTech.

Roth, B. D. (1993). [R-(R*R*)]- 2-(4- fluorphenyl)-beta, delta –dihydroxy-5- (1-methylethyl-3-phenyl- 4[(phenylamino) carbonyl]-1H- pyrrole-1- heptanoic acid, its lactone form and saltstrereof. United States Patent, 1993, Patent No: 5273995.

Supratman, U. (2010). Elusidasi struktur senyawa organik – metode spektoskopi untuk penentuan struktur senyawa organik. Widya Padjajaran. ISBN: 978-602- 8323-50- 519. Tsuge, H., Nishimura, T., Tada, Y., Asao, T., Turk, D. (1999). Inhibition mechanism of cathepsin L-specific inhibitors based on the crystal structure of papain CLIK148 complex. Biochem. Biophys. Res. Commun. 266, pp. 411-416.

Wang, C., Guan, Z., He, Y. (2011). Biocatalytic domino reaction: synthesis of 2H-1-benzopyran-2- one derivatives using alkaline protease from Bacillus licheniformis. Green chemistry, 13 (8), pp. 2048-2054.

Wardencki, W., Curylo, J., Namiesnik, J. (2005). Green chemistry – current and future issues. Polish Journal of Environmental Studies, vol. 14, no. 4, pp. 389-395.

Wen, H., Zhi G., Xiang, D., Yan, H.H. (2012). Enzyme catalytic promiscuity: the papain-catalyzed Knoevenagel reaction. Biochimie, 94, 656-661.

Xie, B. H., Guan, Z., He, Y. H. (2012). Promiscuous enzyme-catalyzed Michael addition: synthesis of warfarin and derivatives. J. Chem. Technol. Biotechnol,. 87, 1709-1714.

Zhi, W., Chun, Y. W., Hao R. W., Hong, Z., Ya, L. S., Teng, F. J., Lei, W. (2014). Lipase-catalyzed Knoevenagel condensation between α,β-unsaturated aldehydes and active methylene compounds. Chinese Chemical Letters, 25, pp. 802-804.



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