5466-88-6

Usage

Uses

Used in Pharmaceutical Industry:
2H-1,4-Benzoxazin-3(4H)-one is used as a key intermediate for the preparation of benzoxazinone/benzothiazinone analogs of fluconazole, which exhibit antifungal and anti-Candida activities. This makes it a valuable compound in the development of new antifungal agents to combat Candida infections.
Used in Drug Development:
2H-1,4-Benzoxazin-3(4H)-one is also used to synthesize 1,4-benzoxazine derivatives with vasorelaxant activities. These derivatives have potential applications in the treatment of cardiovascular diseases, as they may help in the relaxation of blood vessels and improvement of blood flow.

Synthesis Reference(s)

Synthesis, p. 851, 1984 DOI: 10.1055/s-1984-30993

InChI:InChI=1/C8H7NO2/c10-8-5-11-7-4-2-1-3-6(7)9-8/h1-4H,5H2,(H,9,10)

Synthetic route

(2-chloro-phenoxy)-acetic acid amide (35368-68-4) → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

Conditions	Yield
With chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II); caesium carbonate In 1,4-dioxane at 110℃; for 2h; Schlenk technique; Inert atmosphere; chemoselective reaction;	99%

glycolamide (598-42-5) + 1,2-dichloro-benzene (95-50-1) → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

Conditions	Yield
With copper acetylacetonate; sodium hydroxide; N,N`-dimethylethylenediamine In dichloromethane; N,N-dimethyl-formamide at 60℃; for 5h; Reagent/catalyst;	97.6%

2-Iodophenol (533-58-4) + Chloroacetamide (79-07-2) → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

Conditions	Yield
With copper(l) iodide; 1,10-Phenanthroline; caesium carbonate In 1,4-dioxane at 90℃; for 24h; Inert atmosphere;	95%

methanol (67-56-1) + ethyl (2-hydroxyphenyl)carbamate (56836-51-2) → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

Conditions	Yield
With silica gel; potassium nitrate for 0.333333h; Reagent/catalyst; Concentration; Microwave irradiation;	93.6%

chloroacetyl chloride (79-04-9) + 2-amino-phenol (95-55-6) → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

Conditions	Yield
With sodium hydrogencarbonate In water for 4h; Reflux;	93%
With potassium carbonate In acetonitrile for 20h; Reflux;	92.7%
With sodium hydrogencarbonate; N-benzyl-N,N,N-triethylammonium chloride In chloroform 1.) 1 h, 0-5 deg C, 2.) 5 h, 55 deg C;	89%

2-(2-nitrophenoxy)acetonitrile (31507-30-9) → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

Conditions	Yield
With iron; acetic acid for 2.5h; Inert atmosphere; Reflux;	93%
With samarium; titanium tetrachloride In tetrahydrofuran at 20℃; for 0.166667h; reductive cyclization;	70%
With iron; acetic acid for 2h; Reflux;

4-methyl-2-pentanone (108-10-1) + 2-amino-phenol (95-55-6) → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

Conditions	Yield
With sodium hydrogencarbonate In water at 0℃; Reflux;	93%

ethyl o-nitrophenoxyacetate (37682-31-8) → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

Conditions	Yield
With iron; acetic acid at 0℃; for 7h; Inert atmosphere; Reflux;	91%
With iron In acetic acid at 0℃; for 7h; Inert atmosphere; Reflux;	91%
With iron In acetic acid at 0 - 20℃; for 2h; Reflux;	74%

N-(2-hydroxyphenyl)-2-chloroacetamide (10147-68-9) → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide for 10h; Reflux;	88%
With potassium carbonate In ethyl acetate at 20℃; for 10h;	84%
With alkali
With potassium carbonate In tetrahydrofuran for 2h; Reflux; Inert atmosphere;	64.8 g
With potassium tert-butylate In dichloromethane; isopropyl alcohol at 0 - 20℃; for 1h;

ethyl bromoacetate (105-36-2) + 2-amino-phenol (95-55-6) → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene; 1-octyl-3-methylimidazolium tetrafluoroborate at 20℃; for 1h; chemoselective reaction;	86%
Stage #1: ethyl bromoacetate; 2-amino-phenol With potassium fluoride In N,N-dimethyl-formamide at 60℃; Stage #2: With hydrogen; palladium on activated charcoal In ethanol at 60℃; under 7600 Torr;	64%

2-(2-nitrophenoxy)-acetic acid methyl ester (7506-93-6) → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

Conditions	Yield
With samarium; titanium tetrachloride In tetrahydrofuran at 20℃; for 0.166667h; reductive cyclization;	75%
With iron In acetic acid at 80℃; for 1h;

6-bromo-3,4-dihydro-2H-1,4-benzoxazin-3-one (24036-52-0) → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

Conditions	Yield
With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; cesium acetate; isopropyl alcohol at 100℃; Schlenk technique; Inert atmosphere;	72%
With [RhCl2(p-cymene)]2; cesium acetate In isopropyl alcohol at 20 - 100℃; for 24h; Inert atmosphere;	72%

Chloroacetamide (79-07-2) + o-halophenol → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

Conditions	Yield
With potassium carbonate In ethanol for 3h; Heating;	70%

N-(acetoxy)-2-phenoxyacetamide → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

Conditions	Yield
With polyphophoric acid at 65℃; for 2h; Reagent/catalyst; Temperature;	56%

2-Bromoacetyl bromide (598-21-0) + 2-amino-phenol (95-55-6) → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

Conditions	Yield
Stage #1: 2-amino-phenol With potassium carbonate In dichloromethane at 0℃; for 0.5h; Stage #2: 2-Bromoacetyl bromide In dichloromethane at 20℃; for 4h;	55%

N-(benzoyloxy)-2-phenoxyacetamide → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

Conditions	Yield
With polyphophoric acid at 60℃; for 2h; Reagent/catalyst; Temperature;	52%

(E)-3-benzylidene-4-tosyl-3,4-dihydro-2H-1,4-benzoxazine (1232133-30-0) → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

Conditions	Yield
With naphthalene; sodium In tetrahydrofuran at -65℃; for 0.333333h; stereoselective reaction;	50%

6-chloromethyl-4-methyl-3-oxo-2,3-dihydro-4H-1,4-benzoxazine (139503-05-2) + N-methylbenzylamine hydrochloride (13426-94-3) + chloroacetyl chloride (79-04-9) + 2-amino-phenol (95-55-6) → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

Conditions	Yield
With sodium hydrogencarbonate; potassium carbonate In diethyl ether; hexane; chloroform	32%

6-chloro-4-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one (13212-63-0) → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

Conditions	Yield
With hydrogen; palladium on activated charcoal	30%

7-chloro-4-hydroxy-2H-1,4-benzoxazin-3(4H)-one (138035-65-1) → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

Conditions	Yield
With hydrogen; palladium on activated charcoal	30%

2-phenoxyacetohydroxamic acid (46120-83-6) → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

Conditions	Yield
With iron(III) chloride In nitromethane at 60℃; for 2h; Reagent/catalyst; Temperature;	30%
Multi-step reaction with 2 steps 1: triethylamine / chloroform / 2 h / 0 - 20 °C 2: polyphophoric acid / 2 h / 60 °C View Scheme
Multi-step reaction with 2 steps 1: dmap / 3 h / 20 °C 2: polyphophoric acid / 2 h / 65 °C View Scheme

N-(2-hydroxyphenyl)-2-chloroacetamide (10147-68-9) + furan-2,3,5(4H)-trione pyridine (1:1) → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

2-nitrophenoxyacetic acid (1878-87-1) → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

Conditions	Yield
With sodium hydroxide; iron(II) sulfate
With iron; acetic acid
With ethanol; platinum Hydrogenation;

2-chloro-N-(2-methoxyphenyl)acetamide (55860-22-5) → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

Conditions	Yield
With aluminium trichloride at 180℃; folgendes Behandeln mit wss. NaOH;

2-acetamidophenoxyacetic acid (1798-12-5) → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

Conditions	Yield
With hydrogenchloride

2-azidocarbonylmethoxy-benzoyl azide (859942-82-8) → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

Conditions	Yield
With hydrogenchloride

2-amino-phenol (95-55-6) → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

Conditions	Yield
With sodium; toluene anschliessend Erwaermen mit Chloressigsaeure-aethylester;
Multi-step reaction with 2 steps 1: Na2CO3 / CHCl3 / 3 h / Ambient temperature 2: K2CO3 / dimethylformamide / 3 h / 80 °C View Scheme
Multi-step reaction with 2 steps 1: benzene 2: alkali View Scheme

6β-[2-(2-nitro-phenoxy)-acetylamino]-penicillanic acid (29603-66-5) → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

Conditions	Yield
With hydrogen; palladium In water

2H-1,4-benzoxazin-3(4H)-thione (14183-51-8) → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

Conditions	Yield
With hydrogenchloride

4-hydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one (69884-05-5) → 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6)

Conditions	Yield
(i) AcCl, NaHCO3, CH2Cl2, (ii) PhOH; Multistep reaction;

3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6) + acetic anhydride (108-24-7) → 4-acetoxy-(2H)-1,4-benzoxazin-3(4H)-one (33252-96-9)

Conditions	Yield
With pyridine for 12h;	100%

3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6) + di-tert-butyl dicarbonate (24424-99-5) → tert-butyl 3-oxo-3,4-dihydro-2H-1,4-benzoxazine-4-carboxylate (221049-50-9)

Conditions	Yield
With dmap In acetonitrile at 20℃; for 48h;	99%
With dmap In tetrahydrofuran Ambient temperature;	96%
With dmap In tetrahydrofuran at 20℃; Acylation;	96%
With dmap In tetrahydrofuran at 20℃; for 3h; Acylation;	96%
With dmap In acetonitrile for 4h;

3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6) + 2-chloropropionyl chloride (7623-09-8) → 6-(2-chloropropanoyl)-2H-1,4-benzoxazin-3(4H)-one (293741-63-6)

Conditions	Yield
With aluminum (III) chloride In 1,2-dichloro-ethane at 20℃; for 12h;	99%

3-chloromethyl-5-methylisoxazole (35166-37-1) + 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6) → 4-((5-methylisoxazol-3-yl)methyl)-2H-benzo[b][1,4]oxazin-3(4H)-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide for 18h; Heating;	99%

3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6) → 1,4-benzoxazine (5735-53-5)

Conditions	Yield
With [RuCl2(N-heterocyclic carbene)(bis[2-(diphenylphosphino)ethyl]amine)]; hydrogen; caesium carbonate In toluene; butan-1-ol at 120℃; under 22502.3 Torr; for 6h; Schlenk technique; Autoclave;	98%
With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; for 2h; Inert atmosphere;	92%
Stage #1: 3,4-dihydro-3-oxo-2H-1,4-benzoxazine With lithium aluminium tetrahydride In tetrahydrofuran Heating / reflux; Stage #2: With sodium hydroxide; water In tetrahydrofuran	79%

3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6) + ethyl bromoacetate (105-36-2) → ethyl 2-(3-oxo-2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)acetate (26673-71-2)

Conditions	Yield
Stage #1: 3,4-dihydro-3-oxo-2H-1,4-benzoxazine With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 0.25h; Stage #2: ethyl bromoacetate In N,N-dimethyl-formamide at 90℃;	98%
With potassium carbonate In N,N-dimethyl-formamide at 50℃; for 3h;	85%
With potassium carbonate In methanol for 4h; Heating;	77.4%
With sodium hydride In N,N-dimethyl-formamide Ambient temperature;	30%
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 12h;

3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6) + phenyl chloroformate (1885-14-9) → phenyl 2,3-dihydro-4H-1,4-benzoxazin-3-one-4-carboxylate (680971-62-4)

Conditions	Yield
With n-butyllithium In tetrahydrofuran at -78℃;	98%
Stage #1: 3,4-dihydro-3-oxo-2H-1,4-benzoxazine With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: phenyl chloroformate In tetrahydrofuran; hexane at 20℃; for 2h;

3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6) + 1,3-chlorobromopropane (109-70-6) → 4-(3-chloropropyl)-2H-1,4-benzoxazin-3(4H)-one (73733-78-5)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 60h;	97%

3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6) + Ethyl 3-bromopropionate (539-74-2) → ethyl 3-(3-oxo-2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)propanoate (23866-14-0)

Conditions	Yield
Stage #1: 3,4-dihydro-3-oxo-2H-1,4-benzoxazine With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 0.25h; Stage #2: Ethyl 3-bromopropionate In N,N-dimethyl-formamide at 90℃;	95%
With potassium carbonate In N,N-dimethyl-formamide for 18h; Heating;	91%
With sodium hydride In N,N-dimethyl-formamide at 20℃; for 3h;	45%

3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6) + 4-nitrobenzaldehdye (555-16-8) → 2-[(4-nitrophenyl)methylene]-2H-1,4-benzoxazin-3(4H)-one

Conditions	Yield
With acetic anhydride; triethylamine for 7h; Heating;	94%

3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6) + MeX → 4-methyl-4H-benzo[1,4]oxazin-3-one (21744-84-3)

Conditions	Yield
With N-benzyl-N,N,N-triethylammonium chloride; potassium carbonate In acetonitrile at 60℃;	94%

3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6) + Bromoacetaldehyde diethyl acetal (2032-35-1) → 4-(2,2-diethoxyethyl)-1,4-benzoxazin-3-one (1407395-24-7)

Conditions	Yield
Stage #1: 3,4-dihydro-3-oxo-2H-1,4-benzoxazine With potassium tert-butylate In N,N-dimethyl acetamide at 20℃; for 0.0833333h; Stage #2: Bromoacetaldehyde diethyl acetal With tetra-(n-butyl)ammonium iodide In N,N-dimethyl acetamide at 80℃; for 2h;	93.7%

3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6) + isonicotinoyl chloride hydrochloride (39178-35-3) → 6-(1-pyridin-4-ylmethanoyl)-4H-benzo[1,4]oxazine-3-one hydrochloride (1399854-48-8)

Conditions	Yield
With aluminum (III) chloride In N,N-dimethyl-formamide at 85℃; Friedel-Crafts Acylation; Inert atmosphere;	93%

3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6) + propargyl bromide (106-96-7) → 4-(prop-2-yn-1-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (37988-92-4)

Conditions	Yield
With potassium carbonate In acetone for 5h; Heating;	92%
With tetra-(n-butyl)ammonium iodide; potassium carbonate In N,N-dimethyl-formamide at 20℃; for 3h; Cooling with ice;	92%
With potassium carbonate In acetone; toluene Reflux;	75%
With potassium tert-butylate 1.) DMF, RT, 10 min, 2.) RT, 30 min; Yield given. Multistep reaction;
With potassium carbonate In acetone Inert atmosphere; Reflux;

1,4-dibromo-butane (110-52-1) + 3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6) → 4-(4-Bromobutan-1-yl)-3,4-dihydro-2H-1,4-benzoxazin-3(4H)-one (116936-86-8)

Conditions	Yield
With potassium carbonate; potassium iodide In acetonitrile at 100℃;	92%
Stage #1: 3,4-dihydro-3-oxo-2H-1,4-benzoxazine With sodium hydride In N,N-dimethyl-formamide; mineral oil at 30℃; for 1h; Cooling with ice; Stage #2: 1,4-dibromo-butane In N,N-dimethyl-formamide; mineral oil at 30℃;	86%
With aluminum oxide; potassium fluoride; potassium iodide In acetonitrile for 5h; Substitution; alkylation; Heating;

3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6) + chloroacetyl chloride (79-04-9) → 6-(chloroacetyl)-2H-1,4-benzoxazin-3(4H)-one (26518-76-3)

Conditions	Yield
With aluminum (III) chloride In dichloromethane for 5.16h; Cooling with ice; Reflux;	91%
With aluminium trichloride In dichloromethane at 20℃; for 12h; Friedel-Crafts reaction;	87.7%
With aluminium trichloride In dichloromethane	86%
With aluminium trichloride
With aluminium trichloride In dichloromethane

3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6) → 2H-1,4-benzoxazin-3(4H)-thione (14183-51-8)

Conditions	Yield
With Lawessons reagent In tetrahydrofuran for 24h; Ambient temperature;	91%
With tetraphosphorus decasulfide; triethylamine In acetonitrile	90%
With tetraphosphorus decasulfide; N-benzyl-N,N,N-triethylammonium chloride; potassium carbonate In 1,2-dichloro-ethane Heating;	90%

3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6) + 4-(2-bromoethyloxy)benzaldehyde (52191-15-8) → (+/-) 4-[2-(3-Oxo-2H-1,4-benzoxazin-4-yl)ethoxy]benzaldehyde

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 10h;	91%

3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6) + pet + 4-(2-bromoethyloxy)benzaldehyde (52191-15-8) → (+/-) 4-[2-(3-Oxo-2H-1,4-benzoxazin-4-yl)ethoxy]benzaldehyde

Conditions	Yield
With potassium carbonate In water; ethyl acetate; N,N-dimethyl-formamide	91%

3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6) + methyl iodide (74-88-4) → 4-methyl-4H-benzo[1,4]oxazin-3-one (21744-84-3)

Conditions	Yield
With sodium hydroxide; N-benzyl-N,N,N-triethylammonium chloride; silica gel In acetonitrile for 0.133333h; Irradiation;	90%
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 2h;	78.12%
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 2h;	78.12%

3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6) + Benzyl bromoacetate (5437-45-6) → benzyl 2-(3-oxo-1,4-benzoxazin-4-yl)acetate

Conditions	Yield
With potassium carbonate In acetonitrile at 60℃; for 36h; Reflux;	90%

3,4-dihydro-3-oxo-2H-1,4-benzoxazine (5466-88-6) + 2-Bromopropionyl chloride (7148-74-5) → 6-(2-bromopropanoyl)-2H-1,4-benzoxazin-3(4H)-one (58819-99-1)

Conditions	Yield
With aluminum (III) chloride In 1,2-dichloro-ethane at 20℃; for 12h;	89%

Upstream product

• 1878-87-1 2-nitrophenoxyacetic acid 
• 1798-12-5 2-acetamidophenoxyacetic acid 
• 95-55-6 2-amino-phenol 
• 14183-51-8 2H-1,4-benzoxazin-3(4H)-thione 
• 771-26-6 4-hydroxy-2H-1,4-benzoxazin-3-one 
• 7732-18-5 water 
• 57245-10-0 4H-benz[1,4]oxazin-3-one; sodium-compound 
• 31507-30-9 2-(2-nitrophenoxy)acetonitrile 
• 37682-31-8 ethyl o-nitrophenoxyacetate 
• 88-75-5 2-hydroxynitrobenzene 
• 533-58-4 2-Iodophenol 
• 79-07-2 Chloroacetamide 
• 1232133-30-0 (E)-3-benzylidene-4-tosyl-3,4-dihydro-2H-1,4-benzoxazine 
• 24036-52-0 6-bromo-3,4-dihydro-2H-1,4-benzoxazin-3-one 

Downstream Products

• 55894-84-3 2-benzylidene-4H-benzo[1,4]oxazin-3-one 
• 63208-65-1 4-benzyl-2H-benzo[b][1,4]oxazin-3(4H)-one 
• 21744-84-3 4-methyl-4H-benzo[1,4]oxazin-3-one 
• 27320-99-6 3,4-dihydro-7-chloro-3-oxo-2H-1,4-benzoxazine 
• 5735-53-5 1,4-benzoxazine 
• 26518-87-6 6-βCarboxyacryloyl-2H-1,4-benzoxazin-3-on 
• 26513-80-4 2-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazine-6-carbonyl)-benzoic acid 
• 23866-15-1 3-(3-oxo-2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)propanoic acid 
• 120543-09-1 6-(4-acetamido-3-nitrobenzoyl)-1,4-benzoxazin-3(4H)-one 
• 120542-90-7 6-(4-fluorobenzoyl)-2H-1,4-benzoxazin-3(4H)-one 
• 26673-71-2 ethyl 2-(3-oxo-2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)acetate 
• 105492-43-1 4-(2-oxo-2-phenylethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one 
• 105492-44-2 4-(2-Oxo-2-p-tolyl-ethyl)-4H-benzo[1,4]oxazin-3-one 
• 105492-45-3 4-[2-(4-Chloro-phenyl)-2-oxo-ethyl]-4H-benzo[1,4]oxazin-3-one 

Relevant academic research and scientific papers

Rational design, synthesis and anti-proliferative evaluation of novel 1,4-benzoxazine-[1,2,3]triazole hybrids

A series of novel 1,2,3-triazole-1,4-benzoxazine hybrids 5a-n were efficiently synthesized employing click chemistry approach and evaluated for anti-proliferative activity against four cancer cell lines such as HeLa (cervical), MIAPACA (pancreatic), MDA-MB-231 (breast) and IMR32 (neuroblastoma). Compounds 5n and 5g exhibited promising anti-proliferative activity with GI50 values ranging from 1.2 to 2.5 μM and 0.1-1.1 μM respectively against all cell lines, like HeLa, MDA-MB-231, MIAPACA and IMR32, while compound 5l showed significant activity against MDA-MB-231 and IMR32 with GI50 values ranging from 1.1 and 1.4 μM. This is the first report on the synthesis and in vitro anti-proliferative evaluation of 1,2,3-triazole-1,4-benzoxazine hybrids.

Nickel(ii) complexes containing tridentate ONCi ligands (i = abnormal N-heterocyclic carbene donors) and their catalytic application in Suzuki-Miyaura coupling reaction

New nickel complexes with tridentate phenoxy-amidate-aNHC donor groups were synthesized from the reactions between nickel acetate and imidazolium ligand precursors in net pyridine. An unusual degradation pathway was observed, leading to imidazole derivatives occupying the fourth coordination sites in these square planar complexes. A new imidazole-coordinated nickel complex was found to be efficient in catalyzing Suzuki-Miyaura cross-coupling with aryl chlorides under 3 mol% of catalyst loading. The catalytic activities were superior to those of its reported normal NHC counterpart. Instead of the common procedure of using additional phosphine, the addition of IMes·HCl significantly enhances the product yields of the catalytic reaction.

Quantitative helix handedness bias through a single Hvs.CH3stereochemical differentiation

A novel chiral aromatic δ-amino acid building block was shown to fully induce handedness in quinoline oligoamide foldamers with the possibility of further increasing the bias by combining multiples of these units in the same sequence. Through its incorporation within the helix, both N- and C-termini are still accessible for further functionalisation.

Design and Synthesis of Some New 1,4-Benzoxazine-Isoxazole Hybrids as In Vitro Anticancer Agents

Abstract: Synthesis of twelve novel regioselective 1,4-benzoxazine-isoxazole hybrids as in vitro anticancer agents via Cu(I) catalyzed one-pot reaction of various terminal alkynes with 3-(3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl)propanal in benign aqueous t-butanol at room temperature is presented herein. Five products have demonstrated promising activity, among those the compound 6f demonstrates outstanding activity towards PC3, A549, MCF-7, and HeLa with IC50 values of 2.61, 3.34, 2.74, and 7.04 μM respectively.

Synthesis, antimicrobial, antioxidant and docking study of novel 2H-1,4-Benzoxazin-3(4H)-One derivatives

A NOVEL series of 1,4-benzoxazinone derivatives were synthesized and characterized using FT-IR , 1H-NMR, 13C-NMR and Mass spectroscopy. These compounds were in vitro screened against several bacterial species gram positive and gram negative as well as Candida albicans and found exhibiting moderate to potent activity. The antioxidant study was confirmed for the synthesized derivatives against 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical. Docking study for the potent compound 8 against glucosamine-6-phosphate synthase , the target enzyme for the antimicrobial agents was explored to explain the interactions of the discovered hits with in the amino acid residues of the enzyme active side. The docking parameters enhanced the activity of new compound as promising antimicrobial agents.

Synthesis, docking, 3-D-qsar, and biological assays of novel indole derivatives targeting serotonin transporter, dopamine D2 receptor, and mao-a enzyme: In the pursuit for potential multitarget directed ligands

A series of 27 compounds of general structure 2,3-dihydro-benzo[1,4]oxazin-4-yl)-2-{4-[3-(1H-3indolyl)-propyl]-1-piperazinyl}-ethanamides, Series I: 7(a-o) and (2-{4-[3-(1H-3-indolyl) -propyl]-1-piperazinyl}-acetylamine)-N-(2-morfolin-4-yl-ethyl)-fluorinated benzamides Series II: 13(a-l) were synthesized and evaluated as novel multitarget ligands towards dopamine D2 receptor, serotonin transporter (SERT), and monoamine oxidase-A (MAO-A) directed to the management of major depressive disorder (MDD). All the assayed compounds showed affinity for SERT in the nanomolar range, with five of them displaying Ki values from 5 to 10 nM. Compounds 7k, Ki = 5.63 ± 0.82 nM, and 13c, Ki = 6.85 ± 0.19 nM, showed the highest potencies. The affinities for D2 ranged from micro to nanomolar, while MAO-A inhibition was more discrete. Nevertheless, compounds 7m and 7n showed affinities for the D2 receptor in the nanomolar range (7n: Ki = 307 ± 6 nM and 7m: Ki = 593 ± 62 nM). Compound 7n was the only derivative displaying comparable affinities for SERT and D2 receptor (D2/SERT ratio = 3.6) and could be considered as a multitarget lead for further optimization. In addition, docking studies aimed to rationalize the molecular interactions and binding modes of the designed compounds in the most relevant protein targets were carried out. Furthermore, in order to obtain information on the structure-activity relationship of the synthesized series, a 3-D-QSAR CoMFA and CoMSIA study was conducted and validated internally and externally (q2 = 0.625, 0.523 for CoMFA and CoMSIA and r2ncv = 0.967, 0.959 for CoMFA and CoMSIA, respectively).

(E)-N'-ARYLIDENE-2-(3-OXO-2,3-DIHYDRO-4H-BENZO[b][1,4]OXAZIN-4-YL) ACETOHYDRAZIDES AND AN ANTICANCER COMPOSITION COMPRISING THE SAME AS AN ACTIVE INGREDIENT

The present invention relates to (E)-Nandprime;-arylidene-2-(3-oxo-2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)acetohydrazide and an anticancer composition comprising the same as an active component. Specifically, (E)-Nandprime;-arylidene-2-(3-oxo-2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)acetohydrazide according to the present invention activates procaspase-3 to promote the conversion to capase-3, thereby being able to be used as a proliferative inhibitor for various cancer cells. A compound according to the present invention is expected to be developed as an active component of a potent anticancer agent.COPYRIGHT KIPO 2020

Intramolecular cyclization of N-hydroxy-2-phenoxyacetamides and 3-phenoxypropanamides

Abstract: A novel route for the preparation of 2H-1,4- benzoxazin-3(4H)one and 1,5 benzoxazepinones by intramolecular cyclization of N-hydroxy 2-phenoxyacetamide and N-hydroxy -3 phenoxypropanamide using PPA and Lewis acid has been discussed. Graphical abstract: [Figure not available: see fulltext. Caption: Preparation of 2H-1,4- benzoxazin-3(4H)one and 1,5 benzoxazepinones by electrophilic aromatic substitution from N-hydroxy 2-phenoxyacetamide and N-hydroxy -3 phenoxypropanamide and their acetyl and benzoyl derivatives using PPA and Lewis acids.]

Design, synthesis and antimycobacterial activity of benzoxazinone derivatives and open-ring analogues: Preliminary data and computational analysis

This study examines in depth benzoxazine nucleus for antimycobacterial property. We synthesized some benzoxazin-2-one and benzoxazin-3-one derivatives, which were tested for activity against a panel of Mycobacterium tuberculosis (Mtb) strains, including H37Ra, H37Rv and some resistant strains. Several compounds displayed a high antimycobacterial activity and the three isoniazid analogue derivatives 8a-c exhibited a MIC range of 0.125–0.250 μg/mL (0.37–0.75 μM) against strain H37Ra, therefore lower than the isoniazid reference drug. Two benzoxazin-2-one derivatives, 1c and 5j, together with isoniazid-analogue compound 8a, also revealed low MIC values against resistant strains and proved highly selective for mycobacterial cells, compared to mammalian Vero cells. To predict whether molecule 8a is able to interact with the active site of InhA, we docked it into the crystal structure; indeed, during the molecular dynamic simulation the compound never left the protein pocket. The more active compounds were predicted for ADME properties and all proved to be potentially orally active in humans.

Synthesis and biological evaluation of potential acetylcholinesterase inhibitors based on a benzoxazine core

With the purpose of expanding the structural variety of chemical compounds available as pharmacological tools for the treatment of Alzheimer's disease, we synthesized and evaluated a novel series of indole-benzoxazinones (Family I) and benzoxazine-arylpiperazine derivatives (Family II) for potential human acetylcholinesterase (hAChE) inhibitory properties. The most active compounds 7a and 7d demonstrated effective inhibitory profiles with Ki values of 20.3 ± 0.9 μM and 20.2 ± 0.9 μM, respectively. Kinetic inhibition assays showed non-competitive inhibition of AChE by the tested compounds. According to our docking studies, the most active compounds from both series (Families I and II) showed a binding mode similar to donepezil and interact with the same residues.