N-benzyl-(3E,5E)-3,5-bis(2-hydroxybenzylidene)-4-piperidone

Abstract

A novel N-benzyl-(3E,5E)-3,5-bis(2-hydroxybenzylidene)-4-piperidone (3), was synthesized in good yield by a condensation reaction of 2-hydroxybenzaldehyde (1) and N-benzyl-4-piperidone (2) under microwave irradiation in the presence of 10% NaOH solution. The chemical structure was assigned on the basis of UV-visible, IR, ¹H-NMR, ¹³C-NMR and mass spectral data.

Curcumin (diferuloylmethane) is an orange-yellow and dietary polyphenolic phytochemical in turmeric (Curcuma longa). In recent decades, curcumin has been shown to exhibit antioxidant [1], anti-inflammatory [2], antiviral [3], antibacterial [4] effects, and thus has potential use against various malignant cancers, diabetes, allergies, arthritis and other chronic illnesses [5,6,7,8]. For the purpose of finding novel derivatives with increased systemic bioavailability and enhanced pharmacological activity [9], chemical modifications as well as synthesis of curcumin analogues have been attempted by many research groups to find a better treatment for various diseases [9,10]. Analogous compounds to (E)-3,5-bis(benzylidene)-4-piperidones presented noteworthy cytotoxic activity against leukimia cell lines and colon cancer among others [11]. Different substituents with opposing electronic properties in the benzene rings were designed to investigate and discuss the structure–activity relationship [12]. During the course of our continuing search for novel curcumin analogues, we synthesized and characterized 3,4-bis(2-hydroxybenzylidene)-4-piperidone [13]. In this work, we prepared and characterized N-benzyl-(3E,5E)-3,5-bis(2-hydroxybenzylidene)-4-piperidone.

Experimental Section

Synthesis of N-Benzyl-(3E,5E)-3,5-bis(2-hydroxybenzylidene)-4-piperidone (3)

Melting points were determined on an Electrothermal melting point apparatus and are uncorrected. The UV spectra were obtained on a UV Ultraspec 3000 Pro spectrophotometer. The IR spectra were recorded on a Perkin-Elmer 1760X FT-IR (Waltham, MA, USA) in KBr. The mass spectra were recorded with a JEOL JMS-700 (Tokyo, Japan) and a SynaptG2 mass spectrometer (Waters, Milford, MA, USA). ¹H and ¹³C-NMR spectra were recorded with an Agilent DD2 system (Santa Clara, CA, USA) operating at 500 (¹H) and 125 (¹³C) MHz, using residual (δ_H 7.26) and deuterated solvent (δ_C 77.0) peaks of CDCl₃ as reference standards. For synthesis used Mas-II Sineo Microwave. Chromatographic separations were carried out on silica gel 60 (Merck, Darmstadt, Germany). TLC plates were precoated with silica GF₂₅₄ (Merck, 0.25 mm) and detection was achieved by spraying with 10% H₂SO₄ in ethanol, followed by heating.

The title compound was synthesized by mixing the corresponding N-benzyl-4-piperidone (1.89 g, 0.01 mol), 2-hydroxybenzaldehyde (2.44 g, 0.02 mol), 40% aq. NaOH (0.7 mL) and 95% EtOH (5 mL) and was stirred at room temperature for 30 minutes, according to the partially modified procedure of a previous report [9], as shown in Scheme 1. 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 ethyl acetate–methanol to afford 3 (3.58 g, 90%) as an orange crystal, m.p: 143–144 °C. UV (MeOH) λ_max: 306 nm (ε 4,600) and 357 nm (ε 5,200).

IR (KBr) ν_max cm⁻¹: 3235, 3064, 1706, 1661 and 1604.

¹H-NMR (Agilent DD2, 500 MHz, CDCl₃): δ (ppm) 8.90 (2H, s), 8.00 (2H, s), 7.40 (2H, d, J = 8.0 Hz), 6.90 (2H, d, J = 7.5 Hz), 6.80 (2H, d, J = 8.0 Hz), 6.70 (2H, d, J = 7.5 Hz), 3.83 (2H, s), 3.71 (4H, s).

¹³C-NMR (125 MHz, CDCl₃): δ (ppm) 187.4, 157.6, 139.1, 134.0, 132.0, 131.3, 131.0, 129.8, 129.1, 127.9, 123.4, 120.1, 116.6, 62.1, 55.6.

HR-ESI-TOFMS: calculated for C₂₆H₂₄NO₃ m/z 398.1756, found [M + H]⁺, m/z 398.1750.