Process for the synthesis of curcumin-related compounds

A process for the synthesis of curcumin-related compounds comprising the sequential steps:

• A. In a chemically inert, highly polar, aprotic solvent, reacting a suitable complexing agent with a 2,4-diketone of the general structure RCH.sub.2 --CO--CH.sub.2 --CO--CH.sub.2 R in order to produce a stable enolic reactant with the general structure RCH.sub.2 --C(OH).dbd.CH--CO--CH.sub.2 R, in which the R groups are independently selected from H and C.sub.1-12 hydrocarbyl groups selected from alkyl, aryl, aralkyl, alkaryl groups and mixtures thereof;
• B. To the reaction from step A, adding aromatic aldehyde in sufficient amount to effect complete reaction of all of the stable enolic reactant in the solution;
• C. While maintaining the liquid solution from step B at a temperature of at least 40.degree. C., admixing therein catalyst selected from the group consisting of organic primary amines, secondary amines and mixtures thereof to effect condensation of the aldehyde with the enolic reactant, with the concomitant formation of curcumin-related compound, intermediate compounds, water and other reaction by-products and continuing the reaction until all of the enolic reactant in the reaction mass has been consumed, provided further that (1) if the amine catalyst is added incrementally, the total amount thereof is 20-45 mole percent of the enolic reactant or (2) if the entire amine catalyst is added at the beginning of step (1), the concentration thereof is 0.015-0.50 molar;
• D. Admixing the reaction mass from step C with dilute aqueous acid to effect neutralization of any organic amine catalyst which is present, precipitation of the curcumin-related compound in crystalline form and solubilization of unreacted materials;
• and
• E. Separating the precipitated curcumin-related compound from the acidic reaction mass of step D.