Principal Component Analysis Based Solvent Map for Optimisation of Rate and Yield of Curcumin Synthesis

Abstract

Curcumin, a diarylheptanoid normally isolated from Curcuma longa with multiple bioactivities, was synthesized from vanillin and pentane-1,4-dione as initial substrates, n-butylamine as a catalyst, boron oxide as a protecting agent, and tri-n-butyl borate as a water scavenger. The solvents play crucial roles in the reaction rate and the yield of curcumin synthesis. Applying principal component analysis (PCA) method on 89 molecular descriptors calculated for a set of 272 organic solvents, a two-dimensional solvent map was established. Two first principal components, which were found to characterize polarity and polarizability of solvents, accounted for 60% of the data variation and were used as the ordinates of the solvent map. Five solvents, including nhexane, N,N-dimethylacetamide, n-butyl acetate, chloroform and isopropanol, were selected from different areas of the solvent map to investigate the solvent effects on the rate and the yield of curcumin synthesis. The experimental results revealed that the highest formation rate and yield of curcumin were obtained in N,N-dimethylacetamide. The results offered direction for further explorations of the solvent map, in which N,N-dimethylacetamide should be used as a reference to find the optimum solvent for the synthetic procedure of curcumin.