Synthesis and Tautomerism of Curcumin Derivatives and Related Compounds

1,7-Bis(4′-hydroxy-3′-trifluoromethoxyphenyl)-1,6-heptadiene-3,5-dione (2a), related to curcumin, and thirteen 4-substituted derivatives were prepared and their keto/enol ratio in DMSO[D6] was determined by 19F NMR because the enolic form of these related curcumins had been shown to bind to amyloid plaques in the Alzheimer brain. The parent compound and the 4-ethoxycarbonyl derivative were almost 100 % in the enolic form that contains a conjugated hepta-1,4,6-trien-3-on-5-ol backbone. Enolisation decreased to varying amounts in the derivatives that had 4-substituted alkyl groups. Attempts to prepare the 4-hydroxypropyl derivative by hydrolysis of O-methoxymethyl 2m or O-tetrahydropyranyloxy 2n protected derivatives led to cyclised products. A related pyrimidine compound 6b that mimicked a fixed enol form was also prepared.