Amberlite IR-120 H + Resin , an Efficient and Recyclable Solid Phase Catalyst for the Synthesis of 2 , 3-Disubstituted Quinazolin-4 ( 3 H )-Ones : A Greener Approach

A highly efficient synthesis of 2,3-disubstituted quinazolin-4(3H)-ones via Amberlite IR 120 H+ resin. Amberlite IR 120 H+ is a commercially available, heterogeneous and recoverable catalyst to synthesize the 2,3-disubstituted quinazolin-4(3H)-ones in excellent yields.

Evodiamine (Fig. 1, entry-B), is a quinazolincarboline alkaloid isolated from the fruit of Evodia rutaecarpa which is widely utilized in Chinese medicine as an antidote for several health disorders such as resisting tumour, antinociception, weight loss, protecting heart and reducing blood pressure.
Previously, these type of compounds were synthesized by using silica-sulfuric acid 13 , p-TSA 14 , Magnetic Fe3O4 Nanoparticles 15 , Montomorillonite K10 16 .Amberlite IR 120 His Industrial Grade Strong Acid Cation Exchange Resin.It was previously used for various chemical transformations [17][18][19] .It is a nonhazardous and cheap catalyst.In the present invention we prepared various 2, 3-disubstituted quinazolin-4(3H)-ones by using Amberlite IR-120 H + Resin in good yields.So the Amberlite IR 120 H + was found to be the best recoverable heterogeneous catalyst for the synthesis of Quinazoline-4(3H)-one derivatives.

RESULTS AND DISCUSSION
Total 11 number of quinazoline-4(3H)-one derivatives were synthesized by treating isatoic anhydride with different aldehydes and amines as mentioned in the table-1.The obtained products were confirmed by NMR, IR and Mass.

Plausible mechanism
A step wise possible mechanism for the formation of 2, 3-disubstituted quinazolin-4(3H)ones 7 is illustrated in Fig. 2. The primary amine attack on carbonyl group of isatoic anhydride 1, followed by ring opening and decarboxylation provided the amide compound 2. The Nucleophile attack of amine to a carbonyl group of aldehyde and further dehydration under acidic medium provided the compound 4. Compound 5 cyclization and oxidation under air balloon to provided them as a solid compound 7.

Experimental section
All the reagents used in the present work were of Analytical Reagent/ Laboratory Reagent grade.The 1 H and 13 C NMR spectra were determined in CDCl 3 /DMSO-d 6 solution using Varian Gemini 2000 model 200MHz instrument and Oxford magnet Varian Mercury 400MHz instrument.The 1 H chemical shift values were reported on the d scale in ppm, relative to TMS (d= 0.00 ppm), while 13 C chemical shifts relative to CDCl 3 and DMSO-d 6 (d = 39.5 ppm) as internal standards.Spin multiplicities are given as s (singlet), d (doublet), t (triplet) and m (multiplet) as well as br (broad).Coupling constants (J) are given in hertz (Hz).
Mass spectra were run on an Agilent 1100 series LC system coupled to a triple quadrupole mass spectrometer (Agilent LC/MS/MS model 6410, Agilent Technologies Inc., Santa Clara, CA, USA) with electrospray ionization (ESI) source.The highresolution mass spectra (HRMS) were determined using Waters LCT Premier time-of-flight mass spectrometer (Milford, USA) with ESI source.
Infrared spectra (IR) for all samples were recorded on Perkin Elmer 1650 FT IR spectrometer.All reactions were monitored by thin layer chromatography (TLC) on silica gel plates (60 F 254 ), visualizing with ultraviolet light or iodine spray.Column chromatography was performed on silica gel (230-400 mesh) using distilled petroleum ether and ethyl acetate.

General procedure for the synthesis of disubstituted quinazolin-4(3H)-ones
In a 25 mL round bottom flask, isatoic anhydride (1.0 mmol), aldehyde (1.0 mmol), amine (1.1 mmol), Amberlite IR-120 H + resin (300 mg) and water + Acetonitrile (20 mL) were heated to reflux under air balloon for 5 to 8 h.The progress of the reaction was monitored by TLC.After completion of the reaction, the mixture was cooled to room temperature, water (20 mL) and ethyl acetate (20 mL) were added and stirred for about 10 min, filtered and washed with ethyl acetate (20 mL) and both layers separated.The organic layer was washed with water (20 mL) and 10 %NaCl solution.The organic layer was dried with anhyd Na 2 SO 4 , and concentrated under reduced pressure.The crude mass was recrystallized using methanol to afford the products in good yields (3a to 3k).The catalyst was recovered by washing with fresh water (2-3 times) and dried in vacuum oven at 50°C then it was reused for another cycle.