Reactivity of 4H-3,1-benzoxazin-4-ones towards nitrogen and carbon nucleophilic reagents: applications to the synthesis of new Heterocycles

Abstract

6,8-Dibromo-(4H)-3,1-benzoxazinone 1a was synthesized and allowed to react with some nitrogen nucleophiles namely, hydroxylamine hydrochloride, 4-aminoacetophenone, ophenylenediamine, sulfanilamide, sulfamethoxazole, semicarbazide hydrochloride and ethanolamine to afford 3-substituted-4(3H)-quinazolinones 2-8, 10-12 and triazolo[2,3-c]quinazoline 9. 6-Bromo(4H)-3,1-benzoxazin-4-one 1b was also synthesized and converted into 3-amino-4(3H) quinazolinone 13 by reaction with hydrazine hydrate. The latter product was utilized to construct new heterocyclic systems namely, triazino[2,3-c] quinazoline 14 and the thiazole derivative 16. An interesting heterocyclic transformation occurred on treatment of benzoxazinone 1a with malononitrile in presence of sodium ethoxide to give quinoline derivative 18 which reacted with phenyl isocyanate to yield oxazinoquinoline 19. The reaction of benzoxazinone 1a with Grignard' reagents afforded unexpected products 20 and 21 whereas Friedel-Crafts reaction of the same oxazinone with some aromatic hydrocarbons namely, benzene, ethylbenzene, m-and p-xylenes afforded either two benzophenone derivatives 20 and 22 or 23 and 24 in case of less bulky hydrocarbons i.e., benzene and ethylbenzene or only one product 25 and 26 in case of more bulky m-and p-xylenes. Oxazinone ring cleavage occurred when barbituric and/or thiobarbituric acid reacted with benzoxazinone 1a in refluxing pyridine to give the corresponding 5-arylidene derivatives 27a,b.

Fischer indolisation ofN-(α-ketoacyl)anthranilic acids into 2-(indol-2-carboxamido)benzoic acids and 2-indolyl-3,1-benzoxazin-4-ones and their NMR study

“…Smooth reactivity of the 3,1-benzoxazin-4-ones towards different nucleophiles is well documented. 26,28 In our case the reactivity of compound 4f towards phenylhydrazine to form 5f was independently confirmed in boiling toluene as the reaction solvent (Table 5). Analogously, treatment with n-butylamine gave the appropriate amide 6f.…”

“…Pale yellow microneedles, yield 761 mg (78%), mp 173-178 °C (ethyl acetate-benzene), R f = 0.73 (10% ethanol in chloroform). 1 H NMR (500 MHz, DMSO-d 6 ) δ 1.02 (t, 3H, J = 5 Hz), 2.37-2.52 (m, 2H, CH 2 ), 3.23 (s, 3H), 6.49 (d, 2H, J = 10 Hz), 6.67 (dd, 1H, J = 7.5, 7.5 Hz), 7.01 (dd, 2H, J = 7.5, 7.5 Hz), 7.28 (dd, 1H, J = 7.5, 7.5 Hz), 7.45 (d, 1H, J = 7.5 Hz), 7.63 (ddd, 1H, J = 7.7, 7.7, 1.6 Hz), 7.76 (d, 1H, J = 10 Hz), 9.15 (br s, 1H), 12.94 (br s, 1H); 13 C NMR (126 MHz, DMSO-d 6 ) δ 10.0, 18.8, 38.4, 112.9, 119.5, 126.3, 127.8, 128.4, 129.3, 131.0, 132.8, 139.9, 144.5, 146.0, 166.5, 166.8; IR (cm −1 ): ν 3326 m, 1707 s, 1619 s, 1598 s, 1577 s, 1454 m, 1392 m, 1256 s, 1203 m, 760 m, 747 m, 694 m; MS (EI) m/z (%): 325 (1, [M] + ), 174 (100), 151 (24), 146 (24), 145 (34), 105 (28), 104 (26), 91 (34), 77 (37), 43 (25). Found: C, 66.2; H, 5.9; N, 12.7.…”

Phthalazines and phthalazine hybrids as antimicrobial agents: Synthesis and biological evaluation

“…In addition, dihydroisoquinoline derivative 11 was readily obtained through the reaction between benzoxazinone 3 and acetylacetone as a carbon nucleophile (Scheme 2). 36,37 The structure of compound 11 was confirmed by spectroscopic analysis. The IR spectrum exhibited strong absorption bands at 1735 and 1666 cm −1 attributed to three carbonyl groups, and at 1600 cm −1 corresponding to a cyclic imine C=N.…”

Applications of Oxone® in Organic Synthesis: An Emerging Green Reagent of Modern Era

“…The 4H-3,1-benzoxazin-4-one and its congeners are crucial skeletons due to their pharmaceutical activity and to date, many powerful strategies have been reported for the synthesis of benzoxazinones in order to improve the yields and also to mitigate the cost of the reaction vessel. [283][284][285] To further explore the synthesis of these systems to higher level, Munusamy et alpresented an oxidative cyclization of 2-aminobenzoic acid 340 and arylaldehydes 341 to furnish the aryl 4H-3,1-benzoxazin-4-ones 342 a-h using iodine/oxone in reasonable yields as can be seen from an inspection of the Scheme 112. [286] Interestingly, this methodology fruitfully provided the substituted aryl 4H-3,1-benzoxazin-4-ones 342 a-h in decent yields and also have several advantages for example: a) easy availability of starting material, b) transition metal-free approach, c) use of an environmentally benign oxidant, and d) broad substrates scope.…”