The crystal structure of ethyl 2′-hydroxy-4′,6′-dimethoxy-3-(4-methoxynaphthalen-1-yl)-5-oxo-2,3,4,5-tetrahydro-[1,1′-biphenyl]-4-carboxylate, C₂₈H₂₈O₇

Source of material

To a solution of 4,6-dimethoxy-2-hydroxyacetophenone (20 mmol, 3.32 g) in 100 ml of ethanol was added 4-methoxy-1-naphthaldehyde (20 mmol, 3.72 g) and the temperature was adjusted to around 276–278 K in an ice-bath. To the reaction mixture was added 15 mL of 50% (w/v) aqueous KOH solution and the reaction mixture was stirred at room temperature for 24 h. At the end of the reaction, ice water was added to the mixture and it was acidified with 6N HCl (pH = 3–4). The resulting precipitate was filtered and washed with water and ethanol. The crude solid was purified by recrystallization from ethanol to give pure chalcone. An excess amount of ethylacetoacetate (2.6 g, 20 mmol) was added to a solution of the chalcone compound (5 mmol, 1.82 g) in 50 mL anhydrous ethanol, and 5 mL of aqueous NaOH solution was added to the reaction mixture and was refluxed at 360 K for 5 h. The reaction mixture was cooled to room temperature and was acidified with 3N HCl (pH = 3–4). The resulting precipitate was filtered and washed with water and ethanol. The crude solid product was purified by recrystallization from ethanol to afford the title compound (m.p.: 375–377 K; yield: 72%).

Experimental details

Data collections and reduction were carried out using the Bruker software Apex2 and Saint including Sadabs [1]. Hydrogen atoms were placed in their geometrically idealized positions and constrained to ride on their parent atoms.

Comment

Compounds containing a cyclohexenone moiety have been reported to inhibit acetylcholinesterase (AChE) [5], attenuate heart failure in a zebra fish model [6] and show anticancer activities in HCT116 human colon cancer cells [7]. Since cyclohexenone derivatives exhibit various biological activities, the title compound was designed and synthesized according to a previous report [8].

The molecular structure of the title compound is shown in the Figure. The central cyclohexenone ring (C9–C14) has an envelope conformation with the atom C13 as the flap. The benzene ring (C1–C6) and the naphthalene ring system (C18–C27) are attached to the central cyclohexenone ring (C9–C14) at positions C9 and C13, respectively. The dihedral angle between the benzene and ring (C1–C6) and the naphthalene ring system (C18–C27) is 65.03(3)°. The hydrogen atom H13 attached to C13 forms a trans diaxial conformation with each one of H12 atom of the C12 (H12–C12–C13–H13 = −177.2°) and H14A atom of the C14 methylene group (H14A–C14–C13–H13 = −176.1°). The hydrogen atom H13 forms a gauche conformation with the other methylene hydrogen atom H14B (H14B–C14–C13–H13 = −58.4°). The methoxy group at the ortho and para position of the benzene ring are almost coplanar with the ring [C6–C5–O3–C8 = 179.8(2)°, C2–C3–O2–C7 = 3.0(4)°]. However, the methoxy group on the naphthalene ring is tilted from the ring [C20–C21–O7–C28 = 9.1(4)°]. In the crystal, molecules are linked by pairs of O1–H1⋯O5 interactions forming inversion dimers. There are also C–H⋯O interactions present and the dimers are linked via C7–H7B⋯O4 hydrogen bonds. All derived bond lengths and angles of the title structure are in the typical ranges [9, 10].