Silica Chloride Catalyzed Efficient Synthesis of 2,3-Dihydroquinazoline-4(1h)-Ones Derivatives In Water

Search of expeditious and cost-effective methodologies to replace tedious, low productive traditional methodologies gains its own importance. Now a day’s green methodologies has attract significant attention and environmentally benign, recyclable, chap solid catalysts get ultimate reputation. Such methodology offers to obtained complex pharmaceutically important molecules or intermediate by possibly viable ways. Such methodologies shine with imminent light when water incorporates as solvent, due to its non-toxic, green, cheap nature and biochemical consequence [1,2].


Introduction
Search of expeditious and cost-effective methodologies to replace tedious, low productive traditional methodologies gains its own importance. Now a day's green methodologies has attract significant attention and environmentally benign, recyclable, chap solid catalysts get ultimate reputation. Such methodology offers to obtained complex pharmaceutically important molecules or intermediate by possibly viable ways. Such methodologies shine with imminent light when water incorporates as solvent, due to its non-toxic, green, cheap nature and biochemical consequence [1,2].
Readily accessible solid support catalyst like Silica chloride for the synthesis one pot quinazoline has not attempted. Such solid supported catalyst simplifies the reaction procedure and do not pass on unpleasant toxic residue to environment. Silica, perhaps most easily available substance and extensively used as support in reactions [23]. Much organic reactions and used silica chloride as efficient catalyst [24][25][26][27][28]. In continuation of our previous research work [29] to develop fast, naturally benign, productive methodology for small and fused heterocyclic compounds, we intended to developed facile, efficient, cost-effective and easy workup method for the synthesis of quinazoline derivatives. Here, introduce facile methodology as shown in scheme 1 for syntheses of quinazoline derivatives ( Figure 1).

Experimental
The reagents and solvents were purchased from Alfa aesar and Aldrich Chemical companies and used without further purification. All compounds obtained were describe for open head capillary tube for their melting point and are uncorrected. The samples were analyzed by FT-IR spectroscopy (JASCO FT/IR-460 plus spectrometer). 1 HNMR and 13 CNMR spectra of compounds were recorded on a Bruker DRX-400 Avance instrument in DMSO-d6.

Preparation of Silica-chloride
To a well-stirred silica gel (20 g) in DCM (50 mL) was added to this slow drop wise SOCl 2 (20 g) introduced at room temperature. After stirring for 1-2 hour, the solvent was removed under reduced pressure to dryness. The silica chloride thus obtained was used in the describe experiments as catalyst [28].

General Procedure
In a RBF containing 20 ml of water was added 2-aminobezamide (0.01mol 1.36gm), substituted aldehyde (0.01mol) and portion wise SiO 2 -Cl (2 gm 20 mol%) with stirring. The reaction mixture was stir at room temperature. Progress of reaction was monitor by thin layer chromatography (TLC) using Ethyl acetate-Hexane. After completion of reaction, reaction mixture was filter off and filtrate neutralized by saturated solution of sodium bicarbonate, brine and extracted with ethyl acetate. Organic layer dried on anhydrous sodium sulphate and evaporated in reduced pressure to afford pure product after recrystallization from ethanol. Representative compounds were scan for spectral data and found satisfactory agreement with reported.

Silica Chloride as Reusable Catalyst
Catalyst obtained after filter off from first reaction cycle, and dried at 110°C for 2 hours and used for second cycles. Process was repeated until trace product formation takes place during the course of reaction (Table 2).

Results and Discussions
Series of reactions were performed to optimized reaction condition including amount of catalyst with respect to yield of product. Room temperature and 'on' water was kept as fix reaction parameters. 2-aminobenzamide and p-methoxy benzaldehyde were taken for model reaction and various reaction condition were applied. At began, model reaction was done without catalyst to ensure necessity of catalyst and was found little productive (Table 1). When silica without surface modification introduces as catalyst (Table 1) reaction was fruitful, but yield of reaction was not satisfactory. Good to excellent results obtained after introduction of silica chloride as catalyst. Amount of silica chloride were vary in search of optimum amount of catalyst from 5 mol % to 25 mol %. It was observed that ( Table 1) 20 mol% of catalyst offers optimum product.
Silica chloride catalyst reusability study was performed with model reaction (Table 2). First two cycles offers excellent yield of product and productivity decreases after third cycles. It was observed that when reused at fifth time gave 18% of product, as this reading matches with no-catalyst (Table 1) assumed complete neutralization of efficiency of catalyst and no further reusability were checked. By keeping 20mol% of silica chloride as optimum amount of catalyst further derivatisation were performed. Study of effect of various substituents on the yield of reaction was performed (Table 3). It was observed that electron releasing groups present on aromatic aldehydes offers more conversion of product. p-OCH 3 , p-Br, p-CH 3 were found highly productive, whereas, p-NO 2 benzaldehyde was the less productive substituent. The representative products structures were substantial from their spectral data and found satisfactory agreements with reports in literature [20][21][22][23][24][25][26][27][28][29][30] (Figure  2).     [20] a Isolated yields; Reaction condition: 2-aminobenzamide (0.01 mol), p-methoxy benzaldehyde (0.01 mol), silica-chloride (20mol%), stirred in water (20 ml) at rt.

Conclusion
In conclusion, an efficient and simple method for the synthesis of quinazoline analogues has been described using readily available and cost effective silica chloride as a heterogeneous catalyst. The green reaction profile and mild reaction conditions are main advantage of this method. Reaction takes place at room temperature by simply stirring method, with operational simplicity offers excellent yields.