Synthesis of Dihydroquinazolinone Derivatives Using Fe3O4@GO as an Efficient and Reusable Composite Nanocatalyst

Metal nanoparticles, due to their unusual properties especially the high surfaceto-volume ratio than bulk metal has recently become the focus of intense work. Physical and chemical properties of the particles differ considerably differ from those of the compact solids. On the other hand quinazolinone derivatives are fused organic azaheterocyclic compounds which have attracted considerable attention, because they exhibits a wide range of biological properties such as anti-cancer, anti-inflammatory, anticonvulsant and anti-hypertensive activities. In view of the biological importance of quinazoline and its derivatives, several synthetic strategies have been employed including the reactions of anthranilamide with aldehyde derivatives using acids catalyst. In this research, we have used composite metal-graphene-based nanocatalyst to produce different derivatives of dihydroquinazolines in mild reaction conditions and with easy, simple and economical work-up procedure in good-to-high yields. Also the catalysts could be recycled and reused several times without considerable reduction in its activity.


Results and discussions
First, to optimize the reaction conditions, we carried out the reaction of 2-aminobenzamide (1 mmol) and aldehyde or ketone derivatives (1 mmol) as a model reaction in the presence of different organic solvents (Table 1).The results showed that ethanol was the solvent of choice.The effect of catalyst amount on reaction yield was determined, too (Table 2).A significant improvement was observed and the yield of the2-(3-nitrophenyl)-2,3-dihydro-4(1H)-quinazolinone was enhanced to 60% after stirring the reaction mixture for 1/5 h.The best outcome, in terms of yield and the reaction time was obtained with 60 mg/mmol of graphene-supported metal nanocomposite.The scope and generality of synthesis of dihydroquinazolinone derivatives are well showed with structurally diverse aldehydes or ketone.The results are summarized in Table 3. Table 3. Synthesis of 2,3-dihydroquinazolin-4(1H)-ones in the presence of Fe 3 O 4 @GO.b Isolated yield.
Fig. 2 shows the reusability of the catalyst for the preparation of 2-(3-nitrophenyl)-2,3-dihydro-4(1H)-quinazolinone.The model reaction was carried out under the optimized conditions.After completion of the reaction, the catalyst was extracted by magnetite and washed with acetone.Then used as such for subsequent runs (four times) under the same conditions without significant loss of its catalytic activity.

Materials and methods
All chemicals were purchased from Merck, Fluka and Sigma-Aldrich companies and were used without further purification.All reactions and the purity of quinazoline derivatives were monitored by thin-layer chromatography (TLC) using aluminum plates coated with silica gel F254 plates (Merck) using ethyl acetate and n-hexane as eluents.Melting points were determined in open capillaries using an Electro thermal 9100 instrument.IR spectra were recorded on a Shimadzu FT-IR400s. 1 H NMR spectra were recorded on an Avance Bruker DRX-250MHz.

Synthesis of Fe 3 O 4 @GO
The sample of Fe 3 O 4 /GO was prepared as follows: 0.50 g GO was added in to a 100 mL flask H 2 O of 1.56 g FeCl 3 .6H 2 O and 0.58 g FeCl 2 .4H 2 O under the protection of nitrogen condition for 0.05 h at 90 0 C. Then the ammonia solution was added to adjust the pH to 10.The mixture was stirred at 90 0 C for 2 h and then cooled to room temperature.Finally, Fe 3 O 4 @GO composite was separated from the mixture using a permanent magnet, and rinsed with distilled water until the pH of solution reduced to 7.0, and then dried in vacuum oven at 70 0 C for 12 h.

Characterization of the catalyst
The phase structure of the sample was obtained through X-ray diffraction (XRD) measurement.The diffraction peaks at 2θ = 30.39,36.64,43.66, 53.40, 57.40 specified [15].The FT-IR spectra of GO and Fe 3 O 4 and the Fe 3 O 4 @GO composite are shown in Fig. 1.The peak at 1090, 1380 and 1716 cm -1 corresponds to the C-O stretching vibration.The peak at 1618 cm -1 can be assigned to the aromatic skeletal C=C stretching vibration and the peak at 580 cm -1 correspond to the of Fe-O stretching.

General procedure for the synthesis of quinazolin-4(3H)-ones
Fe 3 O 4 @GO (0.06 g) was added to a solution of 2-aminobenzamide (0.136g, 1 mmol) and benzaldehyde (0.106g, 1 mmol) in 3mL of ethanol under reflux temperature for 2.5 h.After completion of reaction, as indicated by TLC (ethyl acetate/n-hexane 1/2), the catalyst was removed by magnet then washed with acetone and after drying could be ready to use for the next reaction without loss in activity.The crude product was filtered and recrystallized from ethanol to give products in good to high yields.

Conclusion
In summary, we have delineated a highly efficient, and green method procedure for the synthesis of 2,3-dihydroquinazolin-4(1H)-ones of anthranilamide with aldehyde or ketone derivatives using Fe 3 O 4 @GOas catalyst.In other words, the most important feature of described method is use of organic solvent and reusability of the catalyst, increasing yields, reducing reaction time.