Lipase-Catalyzed Condensation Reaction of 4-Nitrobenzaldehyde with Acetyl Acetone in Aqueous–Organic Cosolvent Mixtures and in Nearly Anhydrous Media

Abstract

The nature of the product(s) in lipase-catalyzed reaction of acetyl acetone with 4-nitrobenzaldehyde was found to depend upon the source of lipase and the reaction medium. Mucor javanicus lipase was found to give 70% aldol with 80% enantiomeric excess in anhydrous t-amyl alcohol. A 2:2 adduct was formed by the dimerization of the aldol along with an unsaturated cyclic ether as the side products in varying proportions depending upon the reaction medium and the lipase used.

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GRAPHICAL ABSTRACT

Keywords:

• Aldol condensation
• asymmetric synthesis
• biocatalytic promiscuity
• 1,3-diketones
• lipases
• regioselectivity

ACKNOWLEDGMENTS

The financial support by the Department of Science and Technology, government of India (Grant No. SR/SO/BB-68/2010) is gratefully acknowledged. We thank P. S. Pandey, Department of Chemistry, IIT Delhi, for his suggestions and helpful discussions during this work.

Notes

^a 4-Nitrobenzaldehyde (100 mM), acetylacetone (100 mM), 20 mg lipase formulations were taken in 1 mL of phosphate buffer (50 mM, pH 7.0) containing 30% DMSO and were shaken at 200 rpm at 30 °C. Aliquots were taken out at different time intervals and were analyzed by HPLC.

^b After purification by silica-gel column.

^a Determined by analysis of the crude reaction mixture (by analytical HPLC using Zobax Sil C18 column) of hexane and isopropanol (4:1, v/v) at a flow rate of 1 mL/min and was monitored by UV-diode array detector at 254 nm.

^b After column purification.

^c Determined by chiral HPLC using Chiralcel-ODRH column of the column purified aldol product, and polarimetric studies confirmed a dextrorotation in all the cases.