3,5-Bis(2-hydroxybenzylidene)piperidin-4-one

Abstract

The title compound, 3,5-bis(2-hydroxybenzylidene)piperidin-4-one (3), was prepared via reaction of 2-hydroxybenzaldehyde (1) and 4-piperidone (2) under microwave irradiation in the presence of 10% NaOH solution. The compound was fully characterized from its UV, IR, NMR and MS data.

Curcumin is ubiquitous in many Curcuma species and is the major pigment found in the tumeric plant, Curcuma longa. Chemically, curcumin is a phenolic secondary metabolite known to possess anti-inflammatory [1], antioxidant [2], antiviral, anti-infective and anti-allergic activity [4], as well as anti-HIV [5] and anti-cancer [6] properties. Based on the wide range of its biological activities, curcumin has attracted much interst as a model for new target compounds to be synthesized. However, the isolation of curcuminoids from natural substances is low-yielding (3%–5% of the dry-weight), and in addition, the curcuminoids thus obtained possess limited structural variability. Indeed, this method presents an obstacle to optimize the function of curcumin [7]. Therefore, synthesis of curcumin analogues is a practical alternative to obtain a reasonable amount of material as well as a wider variety of structural features. These observation led to us to synthesize a new curcumin analog from 2-hydroxybenzaldehyde and 4-piperidone under microwave irradiation (Scheme 1).

Experimental

Synthesis of 3,5-Bis(2-hydroxybenzylidene)piperidin-4-one (3)

A mixture of 4-piperidone (0.4960 g, 0.01 mol), 2-hydroxybenzaldehyde (1.2212 g, 0.02 mol), 40% aq. NaOH (0.7 mL) and 95% EtOH (5 mL) was stirred at room temperature for 30 min, according to the partially modified procedure of a previous report [8]. The reaction mixture was subjected to microwave irradiation for 3 min at a power of 180 W and temperature of 60 °C. The reaction product was cooled and cold water was added. The precipitate formed was filtered and recrystallized from mixture of n-hexane-ethyl acetate to afford 3 (1.1128 g, 74%) as dark red crystals, m.p: 138 °C (decomp.). UV (MeOH) λ_max: 316 (ε 6,100). IR (KBr) ν_max cm⁻¹: 3399, 3065, 1796, 1658 and 1600. ¹H-NMR (Agilent DD2, 500 MHz, CDCl₃): δ (ppm) 8.10 (2H, s), 6.87 (2H, dd, J = 7.7, 2.0 Hz), 6.77 (2H, dt, J = 7.5, 2.0 Hz), 6.17 (2H, d, J = 8 Hz), 5.91 (2H, t, J = 7.5 Hz), 3.86 (4H, s), 2.40 (1H, br.s). ¹³C-NMR (125 MHz, CDCl₃): δ (ppm) 187.4, 174.0, 134.8, 130.9, 130.7, 128.9, 125.1, 124.5, 107.0, 49.4. HR-ESI-TOFMS: calculated for C₁₉H₁₈NO₃ [M + H]⁺, m/z 308.1287, found m/z 308.1289.