4442-53-9

Basic information

• Product Name: 2,3-Dihydro-1,4-benzodioxine-5-carboxylic acid
• Synonyms: AKOS BBS-00002750;7,10-dioxabicyclo[4.4.0]deca-1,3,5-triene-2-carboxylic acid;5-CARBOXY-1,4-BENZODIOXANE;1,4-BENZODIOXAN-5-CARBOXYLIC ACID;1,4-BENZODIOXANE-5-CARBOXYLIC ACID;2,3-DIHYDRO-BENZO[1,4]DIOXINE-5-CARBOXYLIC ACID;2,3-DIHYDRO-1,4-BENZODIOXINE-5-CARBOXYLIC ACID;2,3-dihydro-1,4-benzodioxin-5-carboxylic acid
• CAS NO: 4442-53-9
• Molecular Formula: C₉H₈O₄
• Molecular Weight: 180.16
• EINECS: 224-670-0
• Product Categories: Acids and Derivatives;Heterocycles;Benzodiozoles, Benzodioxines & Benzodioxepines;Carboxylic Acids;Acids & Esters;Miscellaneous Compounds;Benzodiozoles, Benzodioxines & Benzodioxepines;Carboxylic Acids;BenzodioxanesHeterocyclic Building Blocks;Building Blocks;Heterocyclic Building Blocks;O-Containing;Others
• Mol File: 4442-53-9.mol
• Article Data: 9

Chemical Properties

• Melting Point: 90-94 °C(lit.)
• Boiling Point: 334.1 °C at 760 mmHg
• Flash Point: 139.3 °C
• Appearance: white to light yellow crystal powder
• Density: 1.376 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.587
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 4.09±0.20(Predicted)
• CAS DataBase Reference: 2,3-Dihydro-1,4-benzodioxine-5-carboxylic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 2,3-Dihydro-1,4-benzodioxine-5-carboxylic acid(4442-53-9)
• EPA Substance Registry System: 2,3-Dihydro-1,4-benzodioxine-5-carboxylic acid(4442-53-9)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36-37/39-36/37/38
• WGK Germany: 3
• Hazardous Substances Data: 4442-53-9(Hazardous Substances Data)

Usage

Chemical Properties

white to light yellow crystal powder

InChI:InChI=1/C9H8O4/c10-9(11)6-2-1-3-7-8(6)13-5-4-12-7/h1-3H,4-5H2,(H,10,11)

Synthetic route

2,3-dihydro-benzo[1,4]dioxine-5-carboxylic acid methyl ester → 2,3-dihydro-1,4-benzodioxine-5-carboxylic acid (4442-53-9)

Conditions	Yield
Stage #1: 2,3-dihydro-benzo[1,4]dioxine-5-carboxylic acid methyl ester With sodium hydroxide In water for 3h; Reflux; Stage #2: With hydrogenchloride In water	97%
With sodium hydroxide for 2h; Reflux;	95%
With methanol; sodium hydroxide In tetrahydrofuran; water at 75℃; for 2h;
With lithium hydroxide In water at 20℃;

2,3-dihydro-benzo[1,4]dioxine-5-carboxylic acid methyl ester → 2,3-dihydro-1,4-benzodioxine-5-carboxylic acid (4442-53-9) + methyl 6,7-dibromo-2,3-dihydrobenzo[b][1,4]dioxine-5-carboxylate

Conditions	Yield
With bromine; acetic acid at 60 - 70℃; for 18h;	A 30% B 32.6%

2,3-Dihydroxybenzoic acid (303-38-8) + ethylene dibromide (106-93-4) → 2,3-dihydro-1,4-benzodioxine-5-carboxylic acid (4442-53-9)

Conditions	Yield
With potassium hydroxide unter Ausschluss von Sauerstoff;
With potassium carbonate In N,N-dimethyl-formamide

methyl-2,3-dihydroxybenzoate (2411-83-8) → 2,3-dihydro-1,4-benzodioxine-5-carboxylic acid (4442-53-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 5 h / Reflux 2: sodium hydroxide / water / 3 h / Reflux View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / acetone / 70 °C / Inert atmosphere 2: methanol; sodium hydroxide / water; tetrahydrofuran / 2 h / 75 °C View Scheme
Multi-step reaction with 2 steps 1.1: caesium carbonate / N,N-dimethyl-formamide / 0.5 h / 20 °C 1.2: 4 h / 80 °C 2.1: sodium hydroxide / 2 h / Reflux View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 12 h / Reflux 2: lithium hydroxide / water / 20 °C View Scheme

2,3-Dihydroxybenzoic acid (303-38-8) → 2,3-dihydro-1,4-benzodioxine-5-carboxylic acid (4442-53-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: sulfuric acid / 10 h / Reflux 2: potassium carbonate / N,N-dimethyl-formamide / 5 h / Reflux 3: sodium hydroxide / water / 3 h / Reflux View Scheme
Multi-step reaction with 3 steps 1: sulfuric acid / 8 h / 90 °C 2: potassium carbonate / acetone / 70 °C / Inert atmosphere 3: methanol; sodium hydroxide / water; tetrahydrofuran / 2 h / 75 °C View Scheme
Multi-step reaction with 3 steps 1.1: sulfuric acid / 8 h / Reflux 2.1: caesium carbonate / N,N-dimethyl-formamide / 0.5 h / 20 °C 2.2: 4 h / 80 °C 3.1: sodium hydroxide / 2 h / Reflux View Scheme
Multi-step reaction with 3 steps 1: sulfuric acid / 12 h / 5 °C / Reflux 2: potassium carbonate / N,N-dimethyl-formamide / 12 h / Reflux 3: lithium hydroxide / water / 20 °C View Scheme

Upstream product

• 303-38-8 2,3-Dihydroxybenzoic acid 
• 106-93-4 ethylene dibromide 
• 214894-91-4 2,3-dihydro-benzo[1,4]dioxine-5-carboxylic acid methyl ester 
• 493-09-4 benzo-1,4-dioxane 
• 124-38-9 carbon dioxide 
• 29668-43-7 2,3-dihydro-benzo[1,4]dioxine-5-carbaldehyde 
• 24677-78-9 2,3-dihydroxybenzaldehyde 
• 2411-83-8 methyl-2,3-dihydroxybenzoate 

Downstream Products

• 38871-41-9 2,3-dihydrobenzo-[b]-1,4-dioxine-5-carbonyl chloride 
• 1186388-69-1 C₂₀H₁₉N₃O₃S 
• 532391-79-0 C₂₂H₂₆N₂O₄ 
• 158504-37-1 methyl 8-amino-2,3-dihydrobenzo[b][1,4]dioxine-5-carboxylate 
• 214894-91-4 2,3-dihydro-benzo[1,4]dioxine-5-carboxylic acid methyl ester 
• 873378-07-5 6-hydroxy-2,3-dihydro-benzo[1,4]dioxin-5-carboxylic acid 
• 1116136-19-6 t-butyl (2,3-dihydrobenzo[b][1,4]dioxin-5-yl)carbamate 

Relevant articles and documents

Synthesis of 2,3-dihydrobenzo[b][1,4]dioxine-5-carboxamide and 3-oxo-3,4-dihydrobenzo[b][1,4]oxazine-8-carboxamide derivatives as PARP1 inhibitors

Poly(ADP-ribose) polymerase 1 (PARP1), a widely explored anticancer drug target, plays an important role in single-strand DNA break repair processes. High-throughput virtual screening (HTVS) of a Maybridge small molecule library using the PARP1-benzimidazole-4-carboxamide co-crystal structure and pharmacophore model led to the identification of eleven compounds. These compounds were evaluated using recombinant PARP1 enzyme assay that resulted in the acquisition of three PARP1 inhibitors: 3 (IC50 = 12 μM), 4 (IC50 = 5.8 μM), and 10 (IC50 = 0.88 μM). Compound 4 (2,3-dihydro-1,4-benzodioxine-5-carboxamide) was selected as a lead and was subjected to further chemical modifications, involving analogue synthesis and scaffold hopping. These efforts led to the identification of (Z)-2-(4-hydroxybenzylidene)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-8-carboxamide (49, IC50 = 0.082 μM) as the most potent inhibitor of PARP1 from the series.

Discovery of 2-((2-chloro-6-fluorophenyl)amino)-N-(3-fluoro-5-(trifluoromethyl)phenyl)-1-methyl-7,8-dihydro-1H-[1,4]dioxino[2′,3′:3,4]benzo[1,2-d]imidazole-5-carboxamide as potent, selective and efficacious microsomal prostaglandin E2synthase-1

The discovery and SAR of potent, selective dioxane-fused tricyclic benz[d]imidazole derivatives as mPGES-1 inhibitor are herein described. Various amide modifications in this series afforded many potent mPGES-1 inhibitors, of which 17d proved to be suitab

Synthesis, biological evaluation, and molecular docking studies of novel 2-styryl-5-nitroimidazole derivatives containing 1,4-benzodioxan moiety as FAK inhibitors with anticancer activity

A series of 2-styryl-5-nitroimidazole derivatives containing 1,4-benzodioxan moiety (3a-3r) has been designed, synthesized and their biological activities were also evaluated as potential antiproliferation and focal adhesion kinase (FAK) inhibitors. Among all the compounds, 3p showed the most potent activity in vitro which inhibited the growth of A549 with IC 50 value of 3.11 μM and Hela with IC50 value of 2.54 μM respectively. Compound 3p also exhibited significant FAK inhibitory activity (IC50 = 0.45 μM). Docking simulation was performed for compound 3p into the FAK structure active site to determine the probable binding model.