Synthesis of 3-substituted 4(3h)-quinazolinones catalyzed by ceric ammonium nitrate

Abstract

The synthesis of 3-substituted 4(3H)-quinazolinones from anthranilic acid, orthoesters, and amines in the presence of ceric ammonium nitrate has been studied. The reaction occurred in a few minutes at room temperature under solvent-free conditions and in excellent yields. The probable conversion mechanism has been discussed.One of the most frequently encountered heterocyclic compounds in medicinal chemistry is 4(3H)-quinazolinone, which exhibits interesting pharmacological activities. A series of methods has been developed previously for the synthesis of 3-substituted 4(3H)-quinazolinones from anthranilic acid, orthoesters, and amines in the presence of various catalysts [1][2][3][4][5][6][7][8]. The drawbacks of these methods are expensive catalyst, high temperature (60-80 o C), long reaction time (20 h), etc. In addition, anilines having strong electron-withdrawing substituents, e.g., Cl and NO 2 , gave generally no products at room temperature in previous reports. Hence, it was of interest to develop a more universal method for the synthesis of these products.During the course of our studies towards the development of green catalytic processes, we found that ceric ammonium nitrate (CAN) as an inexpensive and commercially available catalyst can efficiently catalyze one-pot synthesis of 3-substituted 4(3H)-quinazolinones 4 via triple-component condensation of anthranilic acid 1, orthoesters 2, and amines 3 (Scheme 1). The reaction was carried out under solvent-free conditions at room temperature. The triple-component interaction has been studied in the present work with the aim of extending the scope of reactants and of clarifying the mechanism.First, a blank experiment with anthranilic acid, triethyl orthoformate, and aniline in the absence of a catalyst was investigated. The result showed that only 5% product was obtained after 1 h. Then the scope and limitations of the condensation of anthranilic acid 1, triethyl or trimethyl orthoformate 2, and different substituted arylamines or alkylamine 3 catalyzed by CAN were studied; the results are shown in Table 1. All the reactions proceeded smoothly at room temperature. Both triethyl orthoformate and trimethyl orthoformate

Synthesis of New 2-(N'-Allylidene-hydrazino)quinazolinones and 2-(4,5-Dihydropyrazolyl)-quinazolinones and Their Antimicrobial and Antifungal Activity Screening

“…The first step involves the ring closure reaction to form 2-thioxoquinazoline which in turn converted to 2-hydrazinoquinazoline via nucleophilic addition and then elimination reaction. Amino group of 6 gives 1,4-addition reaction with α,β-unsaturated ketones (7) to afford hydrazone (8) derivatives. Acid catalyzed pyrazole ring formation occurs with subsequent addition of NH group on olefinic bond to give 2-pyrazolylquinazolinones (9).…”

“…The 4-(3H)quinazolinone compounds are a class of heterocyclic compounds that have wide variety of biological activities [1][2][3][4] . The biological importance of these heterocyclics has lead synthetic organic chemists to explore new synthetic routes and thus their syntheses are available in literature [5][6][7] . A brief search on the pharmaceutical activities of quinazolin-4(3H)-ones showed antiinflammatory 8 , antitumor 9 , anti HIV 10 , antibacterial 11 , CNS depressant 12 and anticonvulsant 12,13 activities.…”

Green chemistry approach to the synthesis of 3-substituted-quinazolin-4(3H)-ones and 2-methyl-3-substituted-quinazolin-4(3H)-ones and biological evaluation

“…2-Methyl-quinazolin-4(3H )-ones are usually synthesized from anthranilic acid, which is cyclized to benzoxazinone using acetic anhydride, and subsequently in reaction with different amines, a desired quinazolinone is formed (15). Furthermore, a cyclization of anthranilic acid to quinazolin-4(3H )-ones can be performed in a reaction of anthranilic acid, methyl or ethyl orthoformate and different amines (16)(17)(18). All these reaction utilize different volatile organic solvents or catalysts, which should be avoided to decrease the negative impact on the environment.…”

Cerium(IV) ammonium nitrate catalyzed green synthesis of 2-substituted 2,3-dihydro- quinazolin-4(1H)-ones using a grinding technique

“…The use of this reagent for numerous transformations involving C-C, C-O, C-N, and C-S bond formation has been described [14][15][16][17][18][19][20]. However, application of CAN is limited due to its poor solubility in common organic solvents.…”