Highly active magnetically separable CuFe2O4 nanocatalyst: an efficient catalyst for the green synthesis of tetrahydrofuro[3,4-b]quinoline-1,8(3H,4H) dione derivatives

Ramin Ghahremanzadeh 0 1 2 Zahra Rashid 0 1 2 Amir-Hassan Zarnani 0 1 2 Hossein Naeimi 0 1 2 0 A.-H. Zarnani Reproductive Immunology Research Center, Avicenna Research Institute , (ACECR), Tehran, Islamic Republic of Iran 1 Z. Rashid H. Naeimi (&) Department of Organic Chemistry, Faculty of Chemistry, University of Kashan , 87317 Kashan, Islamic Republic of Iran 2 R. Ghahremanzadeh Nanobiotechnology Research Center, Avicenna Research Institute , (ACECR), Tehran, Islamic Republic of Iran A facile and efficient procedure has been reported for the synthesis of tetrahydrofuro[3,4-b]quinoline-1,8(3H,4H)-diones by the condensation reaction of benzaldehydes, 1,3-cyclohexanediones and anilinolactones in the presence of CuFe2O4 as a reusable nanocatalyst with high catalytic activity in water. The notable advantages of this method are excellent isolated yields, short reaction times, simple workup procedure and little environmental impact. - Multicomponent reactions (MCRs) have emerged as a versatile approach in organic synthesis for the construction of complex structures from simple building blocks, due to Electronic supplementary material The online version of this article (doi:10.1007/s13738-014-0422-x) contains supplementary material, which is available to authorized users. their advantages over the conventional multistep synthesis [1, 2]. Preparation of products in a single step and one-pot, operational simplicity, less time consuming, high atom economy, consuming expensive purification processes are the major advantages of multicomponent reactions [35]. Since Breslow has demonstrated that hydrophobic effects could strongly enhance the rate of some organic reactions and rediscovered the use of water as solvent in organic chemistry in 1980s [6, 7], much attention has been focused on organic reactions in water. The unique properties of water are a desirable solvent for chemical reactions and it is safe, non-toxic, environmentally friendly, high abundance, and cheap compared to organic solvents. The use of water as solvent in organic reactions is one of the current focuses today [810]. Tetronic acid (tetrahydrofuran-2,4-dione) is one of the important heterocyclic units, has a broad spectrum of biological properties such as antifungal [11], antibiotic [1216], insecticidal [17], anticoagulant [1820], antiepileptic [21], analgesic [22] and anti-inflammatory activities [23]. Podophyllotoxin (Fig. 1) is a non-alkaloid toxin lignan extracted from the roots and rhizomes of Podophyllum species [24] that inhibits microtubule assembly [2527]. Although Podophyllotoxin and its derivatives have a long and fascinating history biological properties such as, purgative, antiviral, antihelminthic and antitumor [28, 29], but because of mostly unsuccessful attempts to use it for the treatment of human neoplasia, extensive structural modifications have been performed to obtain more potent and less toxic anticancer agents [3032]. Among them, derivatives of 4-azapodophyllotoxin (Fig. 1), were reported as powerful DNA topoisomerase II inhibitors, substitution of carbon atom at position 4 of podophyllotoxin by nitrogen atom would bring about great changes in the biological profile working through a mechanism of action entirely Fig. 1 Structure of podophyllotoxin and 4-azapodophyllotoxin different from that of the parent natural podophyllotoxin [3336]. Magnetic nanoparticles are a class of nanostructured materials of current interest, due to their numerous applications, such as magnetic resonance imaging [37], drug delivery [38, 39], biomolecular sensors [40, 41], bioseparation [42, 43] and magneto-thermal therapy [44, 45]. In addition, biological and medical applications, magnetic nanoparticles are efficient supports for catalysts in organic synthesis [46, 47], because of their extremely small size and large surface to volume ratio and can facilitate their separation effectively from the reaction media by magnetization with a permanent magnetic field [4851]. In view of the important biological properties of the azapodophyllotoxin derivatives, we report herein a novel and clean synthesis of tetrahydrofuro[3,4-b]quinoline1,8(3H,4H)-dione derivatives through a three-component condensation reaction of benzaldehydes, 1,3-cyclohexanediones and anilinolactones in the presence of CuFe2O4 nanoparticles as magnetically recyclable catalyst in water media. Chemicals and apparatus The chemical used in this work were obtained from Fluka and Merck and were used without purification. Melting points were measured on an Electrothermal 9200 apparatus. IR spectra were recorded as KBr pellets on a PerkinElmer 781 spectrophotometer and an Impact 400 Nicolet FT-IR spectrophotometer. 1H NMR and 13C NMR spectra were recorded in d6-DMSO solvents on a Bruker DRX-400 spectrometer with tetramethylsilane as internal reference. The elemental analyses (C, H, N) were obtained from a Carlo ERBA Model EA 1108 analyzer. XRD analysis was performed with an X-ray diffractometer (PAnalytical XPert-Pro) using a Cu-Ka monochromatic radiation source and a Ni filter. The nanocatalyst was determined using a KYKY EM-3200 scanning electron microscope (SEM) operated at a 26 kV accelerating voltage. The purity determination of the substrates and reaction monitoring were accomplished by TLC on silica-gel polygram SILG/ UV 254 plates (from Merck Company). Typical experimental procedure for the preparation of magnetic nanocatalyst CuFe2O4 nanoparticles were prepared by co-precipitation of Cu(NO3)2 and Fe(NO3)3 in water in the presence of sodium hydroxide. Briefly, to a solution of Fe(NO3)3 9H2O (0.05 mol) and Cu(NO3)2 3H2O (0.025 mol) in 100 mL of distilled water, 75 mL of NaOH 4 M was added at room temperature over a period of 10 min to form reddish-black precipitate. Then the reaction mixture was warmed to 90 C and stirred. After 2 h, it was cooled to room temperature and the formed magnetic particles were separated by a magnetic separator. The catalyst was washed with water and kept in air oven over night at 80 C. Then the catalyst was ground in a mortarpestle and kept in a furnace at 800 C at a heating rate of (2 C/min) and cooled to 100 C at (5 C/ min) in air. [52]. Typical procedure for the preparation of tetrahydrofuro[3,4-b]quinoline-1,8(3H,4H)-dione derivatives To prepare tetrahydrofuro[3,4-b]quinoline-1,8(3H,4H)dione derivatives, to a mixture of benzaldehyde (1 mmol), 1,3-cyclohexanedione (1 mmol), anilinolactone (1 mmol) in water, nano CuFe2O4 (5 mol%) was added and heated under reflux condition. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was cooled at room temperature. The nanoparticles were easily separated from the reaction mixture with an external magnet and reutilized four times for the same reaction. The crude solids were filtered off and washed with water. The pure products were obtained by recrystallization from methanol and were identified by physical and spectroscopic data. 9- (...truncated)