Structures in solid state and solution of dimethoxy curcuminoids: regioselective bromination and chlorination

Abstract

BackgroundSeveral papers described the structure of curcumin and some other derivatives in solid and in solution. In the crystal structure of curcumin, the enol H atom is located symmetrically between both oxygen atoms of the enolone fragment with an O···O distance of 2.455 Å, which is characteristic for symmetrical H-bonds. In the solution, the geometry of the enolone fragment is attributed to the inherent disorder of the local environment, which solvates one of the basic sites better than the other, stabilizing one tautomer over the other. In this paper, how the position of methoxy groups in dimethoxy curcuminoids influence the conformation of molecules and how the halogen atoms change it when they are bonded at α-position in keto-enol part of molecules is described.ResultsSix isomers of dimethoxy curcuminoids were prepared. Conformations in solid state, which were determined by X-ray single crystallography and 1H MAS and 13C CPMAS NMR measurements, depend on the position of methoxy groups in curcuminoid molecules. In solution, a fast equilibrium between both keto-enol forms exists. A theoretical calculation finding shows that the position of methoxy groups changes the energy of HOMO and LUMO. An efficient protocol for the highly regioselective bromination and chlorination leading to α-halogenated product has been developed. All α-halogenated compounds are present mainly in cis keto-enol form.ConclusionsThe structures in solid state of dimethoxy curcuminoids depend on the position of methoxy groups. The NMR data of crystalline solid samples of 3,4-diOCH3 derivative, XRD measurements and X-ray structures lead us to the conclusion that polymorphism exists in solids. The same conclusion can be done for 3,5-diOCH3 derivative. In solution, dimethoxy curcuminoids are present in the forms that can be described as the coexistence of two equivalent tautomers being in fast equilibrium. The position of methoxy groups has a small influence on the enolic hydrogen bond. Theoretical calculations show that the energy gap between HOMO and LUMO depend on the position of methoxy groups and are lower in solution. Chlorination and bromination on α-position of 1,3-diketone moiety do not change the preferential form being cis keto-enol as in parent compounds.

Use of Curcumin, a Natural Polyphenol for Targeting Molecular Pathways in Treating Age-Related Neurodegenerative Diseases

“…Cur can co-exist with several tautomeric forms, of which two predominant forms are 1,3-diketo form and 1,3-dienol form ( Figure 1 E). Although in the solid phase or solution the enol form is more stable, their relative concentrations may vary with temperature, polarity of solvent, pH, and substitution of the aromatic rings [ 16 , 17 ].…”

Synthesis, structure and biological activity of 3(5)-trifluoromethyl-1H-pyrazoles derived from hemicurcuminoids

“…The interest in curcumin [(1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione] [1,2,3,4,5,6,7,8,9] has prompted many structural studies on this β-diketone tautomerism [10,11,12,13,14] as well as on the synthesis and structural studies of hemicurcuminoids, compounds resulting from the replacement of one styryl branch of curcumin (2-methoxy-4-vinylphenol) by a simpler group, for instance, a phenyl group [11,15].…”

Selective photoisomerisation of 2-chloromalonaldehyde

“…This effect has been observed and explained in dimethoxy curcuminoids compounds. 48 The second band around 235 nm corresponds mainly to the majority open conformer detected after deposition, i.e., TTC. 18 This assignment is also in perfect agreement with the theoretical predictions reported in Table I.…”