Nowadays nanoparticles have drawn the attention of scientists, because of their extensive application in the development of new technologies in the areas of electronics,material sciences,catalyst and medicine at the nanoscale ^{[1, 2, 3]}. The development of green processes using agricultural waste for the synthesis of nanoparticles is evolving into an important branch of nanotechnology ^{[4, 5, 6]}. The use of environmentally benign materials like plant leaf extract ^[7],bacteria ^[8],fungi ^[9] and enzymes ^[10] for the synthesis of metal nanoparticles offers numerous benefits such as eco-friendliness and compatibility for pharmaceutical and other biomedical applications as they do not use toxic chemicals in the synthetic protocols. Eco-friendly reagents,catalysts,and reaction medium such as water,supercritical fluids,ionic liquids or solventfree reactions for green chemical approaches have been studied. In this context,metal oxide nanoparticles are attractive candidates as solid supports for the highly active and recyclable catalytic systems. Due to their large surface area,which can carry a high payload of catalytically active species,nanoparticles exhibit very high catalytic activity and chemical selectivity under mild conditions ^[11]. In addition,they can be recovered through a centrifugation or filtration process and reused for the next reaction,combining the advantages of both homogeneous and heterogeneous catalysts. Although many synthetic technologies are present,worldwide the researchers are continuously searching suitable bio-methods for the synthesis of desired nanoparticles ^[12].

Currently,TiO₂ nanoparticles have emerged as an attractive multi-functional material. TiO₂ nanoparticles have unique properties such as high stability,long lasting,safe and broad-spectrum anti-biosis ^[13]. TiO₂ nanoparticles in particular have been the centre of attention because of their photo-catalytic activities. TiO₂ nanoparticles have been used as a green catalyst in many organic reactions ^[14]. One-pot multicomponent reactions become increasingly important in organic and medicinal chemistry. The strategies of MCRs offer significant advantages over conventional linear-type syntheses in terms of high degree of atom economy, convergence,and ease of execution ^[15]. Multicomponent reactions leading to the formation of nitrogen-containing heterocyclic systems such as pyridine and pyrimidine have recently been studied ^{[16, 17]}. The achievement of making multiple bonds in a one-pot multicomponent coupling reaction provides a sustainable synthetic approach in new molecule discovery ^[18].

Quinazolin-4(1H)-ones are important N-heterocyclic compounds having various biological activities ^{[19, 20, 21, 22, 23, 24]}. However, methods for the selective synthesis of 2,3-dihydroquinazolin- 4(1H)-ones have not been explored before. Thus,developing versatile approaches to synthesize 2,3-dihydroquinazolin-4(1H)- ones still remains a highly desired goal in organic synthesis. In our present work of solvent free synthesis of quinazolinone,we utilized bio-inspired TiO₂ NPs as catalyst in the 4(1H)-quinazolinone synthesis. 2. Experimental 2.1. Bio-fabricated TiO₂ nanoparticles

Biosynthesis of rutile TiO₂ nanoparticles (TiO₂ NPs) was achieved by a novel,biodegradable and convenient procedure using fruit peel Annona squamosa aqueous extract. Rutile TiO₂ NPs were characterized using UV,XRD,SEM and TEM studies ^[25]. 2.2. General procedure for synthesis of 2,3-disubstituted 2,3-dihydroquinazolin-4(1H)-ones,4a-g

A mixture of isatoic anhydride,1 (0.234 g,2 mmol),methyl amines,2 (68.7 mL,2 mmol),benzaldehydes 3a-g (2 mmol) and TiO₂ NPs (5 mol%) was heated at 70℃ for 30 min. The reaction was monitored by TLC analysis using petroleum ether-ethyl acetate (1:4,v/v). After the completion of the reaction,the reaction mixture was cooled to room temperature. The solid residue was dissolved in hot ethanol and centrifuged to remove the catalyst. Then the filtrate was subjected to column chromatography eluting with petroleum ether-ethyl acetate (1:4,v/v) to isolate the desired compounds. The isolated compounds were confirmed by FTIR, ¹H NMR,¹³C NMR and GC-MS analyses. 3. Results and discussion

We isolated the 2,3-dihydro-3-methyl-2-phenylquinazolin- 4(1H)-one analogues,4a-g by column chromatography in >90% yield. These products were characterized using FT-IR,¹H NMR,¹³C NMR and mass analyses. Analysis results are given in Supporting information. In FT-IR,compound 4a showed peaks at 3452.58 cm^-1,corresponding to -NH stretching,3265.49 cm^-1 for -NCH₃,and 1622.13 cm^-1 for the -C=O group. In proton NMR, the singlet at δ 2.88 corresponds to methyl protons (-CH₃),the peak at δ 4.48 is corresponding to -NH proton,peak at δ 5.71 is corresponding to -CH proton and peaks at δ 6.52-7.97 belong to aromatic protons. In ¹³C NMR,the methyl group appears at δ 32,- CH group appears at δ 74,aromatic carbons appears at a δ 114-145 and -C=O appears at δ 163. We optimizeded the reaction with various amount (mol%) of TiO₂ NPs. Catalyst concentration plays a major role in the product yields. It was observed that increasing the loading of the catalyst from 2 to 5 mol% gave an improved yield of 91% of the product (Table 1). Further increase of catalyst loading leads to lower reaction yields because the products tend to be absorbed on the catalyst.

Table 1

Table 1 Optimization of the amount of TiO2 NPs in the synthesis of 2,3-dihydro-3-methyl-2-(4-(dimethylamino)phenyl)quinazolin-4(1H)one,4b.

Table 1 Optimization of the amount of TiO2 NPs in the synthesis of 2,3-dihydro-3-methyl-2-(4-(dimethylamino)phenyl)quinazolin-4(1H)one,4b.

In order to elucidate the role of the solvents,various solvents were used in order to evaluate the scope and limitation of the reaction. After screening different solvents,it was found that TiO₂ NPs catalyzed syntheses of quinazolinone were not only faster,but also resulted in better yields under solvent free conditions (Table 2).

Table 2

Table 2 Effect of solvent for the synthesis of 2,3-dihydro-3-methyl-2-(4-(dimethylamino)- phenyl)quinazolin-4(1H)one,4b.

Table 2 Effect of solvent for the synthesis of 2,3-dihydro-3-methyl-2-(4-(dimethylamino)- phenyl)quinazolin-4(1H)one,4b.

In general,the polar protic solvents (EtOH and water) result in good yields. The aprotic solvents (CHCl₃ and DCM) give the lowest yield. The dielectric constant measures the solvent’s ability to reduce the field strength of the electric field surrounding a charged particle immersed in it. The protic solvents have higher dielectric constant values compared with aprotic (non-polar) solvents. The protic (polar) solvents that can donate proton easily can form hydrogen bonds with the reactants. These could be the reasons that we are getting better yields in protic solvents than in aprotic solvents. In Table 3,the results of isatoic anhydride,1 methylamine, 2 with various substituted aromatic aldehydes,3a-g under solvent free conditions using TiO₂ NPs are shown. All products were isolated by column chromatography in good yields (>90%).

Table 3

Table 3 Synthesis of 2,3-disubstituted 2,3-dihydroquinazolin-4(1H)-ones,4a-g.

Table 3 Synthesis of 2,3-disubstituted 2,3-dihydroquinazolin-4(1H)-ones,4a-g.

We have successfully synthesized the TiO₂ nanoparticles using aqueous A. squamosa peel extract. These synthesized TiO₂ nanoparticles were characterized using UV,XRD and TEM. Synthesized TiO₂ nanopowders were used as a catalyst for 2,3-dihydro-3-methyl-2-phenylquinazolin-4(1H)-one analogues,4a-g synthesis. The compounds were purified by column chromatography using petroleum ether-ethyl acetate (75:25,v/v) as eluting solvents. Acknowledgments

We thank the management of VIT University for providing all the facilities to carry out this work. We acknowledge the support extended by VIT-SIF for NMR and GC-MS analysis. Also Dr. S. Mohana Roopan thanks DBT for providing DBT-RGYI project (No. BT/PR6891/GBT/27/491/2012) fund. Appendix A. Supplementary data

Supplementary data associated with this article can be found,in the online version,at http://dx.doi.org/10.1016/j.cclet.2013.11.040.