65145-13-3

Basic information

• Product Name: 2-Fluoro-4-hydroxybenzoic acid
• Synonyms: RARECHEM AL BO 0814;2-FLUORO-4-HYDROXYBENZOIC ACID;4-Carboxy-3-fluorophenol;Benzoicacid, 2-fluoro-4-hydroxy-
• CAS NO: 65145-13-3
• Molecular Formula: C₇H₅FO₃
• Molecular Weight: 156.11
• EINECS: 1806241-263-5
• Product Categories: FINE Chemical & INTERMEDIATES;Aromatic Carboxylic Acids, Amides, Anilides, Anhydrides & Salts;Benzoic acid;Acids & Esters;Fluorine Compounds;Phenols;Fluorine series
• Mol File: 65145-13-3.mol
• Article Data: 10

Chemical Properties

• Melting Point: 199-202
• Boiling Point: 334.6 °C at 760 mmHg
• Flash Point: 156.2 °C
• Appearance: /
• Density: 1.492 g/cm³
• Vapor Pressure: 4.99E-05mmHg at 25°C
• Refractive Index: 1.585
• Solubility: soluble in Methanol
• PKA: 3?+-.0.10(Predicted)
• CAS DataBase Reference: 2-Fluoro-4-hydroxybenzoic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Fluoro-4-hydroxybenzoic acid(65145-13-3)
• EPA Substance Registry System: 2-Fluoro-4-hydroxybenzoic acid(65145-13-3)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 36/37/38-22
• Safety Statements: 26-36
• HazardClass: IRRITANT
• Hazardous Substances Data: 65145-13-3(Hazardous Substances Data)

Usage

Chemical Properties

Pale yellow liquid

Uses

2-Fluoro-4-hydroxybenzoic Acid, is a fluorinated building block used for the synthesis of more complex pharmaceutical and biologically active compounds. It is also fluorine substituted 4-hydroxybenzoates, which has been shown to have antioxidant activity.

InChI:InChI=1/C7H5FO3/c8-6-3-4(9)1-2-5(6)7(10)11/h1-3,9H,(H,10,11)

Synthetic route

2-fluoro-4-hydroxybenzonitrile (82380-18-5) → 2-fluoro-4-hydroxybenzoic acid (65145-13-3)

Conditions	Yield
Stage #1: 2-fluoro-4-hydroxybenzonitrile With sodium hydroxide In water for 4h; Heating / reflux; Stage #2: With hydrogenchloride In water at 20℃;	100%
With sodium hydroxide In water for 60h; Yield given;
With potassium hydroxide In ethanol; water

2-fluoro-4-propoxybenzoic acid → 2-fluoro-4-hydroxybenzoic acid (65145-13-3)

Conditions	Yield
With boron tribromide In dichloromethane at -78 - 20℃;	89%

3-chloro-2-fluoro-4-hydroxybenzoic acid (860296-15-7) → 2-fluoro-4-hydroxybenzoic acid (65145-13-3)

Conditions	Yield
With ammonium formate; palladium on activated charcoal In methanol at 25℃; for 20h;	89%

3-(fluorophenyloxy)triisopropylsilane (860296-18-0) + carbon dioxide (124-38-9) → 2-fluoro-4-hydroxybenzoic acid (65145-13-3) + 6-fluorosalicylic acid (67531-86-6)

Conditions	Yield
Stage #1: 3-(fluorophenyloxy)triisopropylsilane With N,N,N',N'',N'''-pentamethyldiethylenetriamine; sec.-butyllithium In tetrahydrofuran at -75℃; for 2h; Stage #2: carbon dioxide In tetrahydrofuran	A 51% B 5%

2,4-difluoro-benzoic acid (1583-58-0) → 4-fluorosalicylic acid (345-29-9) + 2-fluoro-4-hydroxybenzoic acid (65145-13-3)

Conditions	Yield
With sodium hydroxide for 7h; Heating; Title compound not separated from byproducts;

2-fluoro-4-hydroxy-3-trimethylsilanyl-benzoic acid → 2-fluoro-4-hydroxybenzoic acid (65145-13-3)

Conditions	Yield
With hydrogenchloride In water at 25℃; for 6h;	3.24 g

carbon dioxide (124-38-9) + 3-(methoxymethoxy)-2-(trimethylsilyl)fluorobenzene (146746-69-2) → 2-fluoro-4-hydroxybenzoic acid (65145-13-3)

Conditions	Yield
Stage #1: 3-(methoxymethoxy)-2-(trimethylsilyl)fluorobenzene With n-butyllithium; potassium tert-butylate In tetrahydrofuran; hexane at -75℃; for 2h; Stage #2: carbon dioxide In tetrahydrofuran; hexane Stage #3: With hydrogenchloride In water at 25℃; for 6h;

2-chloro-1-fluoro-3-(methoxymethoxy)benzene (860296-13-5) → 2-fluoro-4-hydroxybenzoic acid (65145-13-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: BuLi; 2,2,6,6-tetramethylpiperidine / tetrahydrofuran; hexane / 2 h / -75 °C 1.2: tetrahydrofuran; hexane 1.3: 73 percent / HCl / H2O / pH 1 2.1: 89 percent / ammonium formate / Pd/C / methanol / 20 h / 25 °C View Scheme

3-fluorophenol (372-20-3) → 2-fluoro-4-hydroxybenzoic acid (65145-13-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 83 percent / imidazole / dimethylformamide / 20 h / 25 °C 2.1: sec-BuLi; PMDTA / tetrahydrofuran / 2 h / -75 °C 2.2: 51 percent / tetrahydrofuran View Scheme
Multi-step reaction with 3 steps 1: 61 percent / bromine / CHCl3 / 0.01 h 2: 1-methyl-2-pyrrolidinone / 2 h / 180 °C 3: sodium hydroxide / H2O / 60 h View Scheme

1-fluoro-3-(methoxy-methoxy)benzene (126940-10-1) → 2-fluoro-4-hydroxybenzoic acid (65145-13-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sec-BuLi / tetrahydrofuran; cyclohexane / 2 h / -75 °C 1.2: 86 percent / tetrahydrofuran; cyclohexane / 0.75 h / -75 °C 2.1: BuLi; KOtBu / tetrahydrofuran; hexane / 2 h / -75 °C 2.2: tetrahydrofuran; hexane 3.1: 3.24 g / HCl / H2O / 6 h / 25 °C View Scheme
Multi-step reaction with 2 steps 1.1: sec-BuLi / tetrahydrofuran; cyclohexane / 2 h / -75 °C 1.2: 86 percent / tetrahydrofuran; cyclohexane / 0.75 h / -75 °C 2.1: K-OtBu; BuLi / tetrahydrofuran; hexane / 2 h / -75 °C 2.2: tetrahydrofuran; hexane 2.3: HCl / H2O / 6 h / 25 °C View Scheme
Multi-step reaction with 3 steps 1.1: sec-BuLi / tetrahydrofuran; cyclohexane / 2 h / -75 °C 1.2: 83 percent / 1,1,2-trichloro-1,2,2-trifluoroethane / tetrahydrofuran; cyclohexane / 0.75 h / -75 °C 2.1: BuLi; 2,2,6,6-tetramethylpiperidine / tetrahydrofuran; hexane / 2 h / -75 °C 2.2: tetrahydrofuran; hexane 2.3: 73 percent / HCl / H2O / pH 1 3.1: 89 percent / ammonium formate / Pd/C / methanol / 20 h / 25 °C View Scheme

3-(methoxymethoxy)-2-(trimethylsilyl)fluorobenzene (146746-69-2) → 2-fluoro-4-hydroxybenzoic acid (65145-13-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: BuLi; KOtBu / tetrahydrofuran; hexane / 2 h / -75 °C 1.2: tetrahydrofuran; hexane 2.1: 3.24 g / HCl / H2O / 6 h / 25 °C View Scheme

4-bromo-3-fluorophenol (121219-03-2) → 2-fluoro-4-hydroxybenzoic acid (65145-13-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1-methyl-2-pyrrolidinone / 2 h / 180 °C 2: sodium hydroxide / H2O / 60 h View Scheme

2-fluoro-2-hydroxybenzonitrile → 2-fluoro-4-hydroxybenzoic acid (65145-13-3)

Upstream product

• 82380-18-5 2-fluoro-4-hydroxybenzonitrile 
• 1583-58-0 2,4-difluoro-benzoic acid 
• 860296-18-0 3-(fluorophenyloxy)triisopropylsilane 
• 124-38-9 carbon dioxide 
• 146746-69-2 3-(methoxymethoxy)-2-(trimethylsilyl)fluorobenzene 
• 394-42-3 2-fluoro-4-methoxy-benzoic acid 
• 331-64-6 2-fluoro-4-methoxy-benzaldehyde 
• 217978-01-3 ethyl-2-fluoro-4-hydroxy-benzoate 
• 121219-03-2 4-bromo-3-fluorophenol 
• 126940-10-1 1-fluoro-3-(methoxy-methoxy)benzene 
• 372-20-3 3-fluorophenol 
• 860296-13-5 2-chloro-1-fluoro-3-(methoxymethoxy)benzene 
• 860296-15-7 3-chloro-2-fluoro-4-hydroxybenzoic acid 
• 203115-96-2 2-fluoro-4-propoxybenzoic acid 

Downstream Products

• 123843-54-9 4-butoxy-2-fluorobenzoic acid 
• 119810-26-3 2-Fluoro-4-hydroxy-benzoic acid 2-methyl-butyl ester 
• 217978-01-3 ethyl-2-fluoro-4-hydroxy-benzoate 
• 521074-57-7 2-fluoro-4-(4-fluorobutoxy)benzoic acid 
• 131034-44-1 4-acetoxy-2-fluorobenzoic acid 
• 197507-22-5 methyl 2-fluoro-4-hydroxybenzoate 
• 136386-10-2 2-fluoro-4-n-tridecanoyloxybenzoic acid 
• 142935-73-7 benzyl 2-fluoro-4-hydroxybenzoate 
• 1227870-23-6 4-(4-pentylbenzoyloxy)-2-fluorobenzoic acid 
• 1210887-74-3 4-cyano-3-fluorophenyl 4-(4-pentylbenzoyloxy)-2-fluorobenzoate 
• 1227870-20-3 benzyl 4-(4-pentylbenzoyloxy)-2-fluorobenzoate 
• 1037776-16-1 3-fluoro-4-(methylthiomethyl)phenol 

Relevant articles and documents

Hydrogen-bonded bent-core blue phase liquid crystal complexes containing various molar ratios of proton acceptors and donors

Various hydrogen-bonded (H-bonded) bent-core liquid crystal complexes consisting of pyridyl and benzoic acid derivatives were synthesized and compared with their covalent analogues in this study. The molar ratios of pyridyl and benzoic acid derivatives could be tuned to form various H-bonded liquid crystal (LC) diads (with 1:1 molar ratio of H-acceptors T and H-donors D) and complexes (with different molar ratios of T and D). By insertion of H-bonds into different positions of bent-core supramolecules, the mesophasic properties of H-bonded bent-core LC complexes were optimized, which could facilitate the most suitable LC components and compositions to be utilized in H-bonded blue phase (BP) LC complexes. In BPLC complexes, the molar ratios, alkyl chain lengths, the lateral fluoro-substitution and the chiral center of H-bonded bent-core supramolecules would affect the temperature ranges of BPs. Accordingly, H-bonded bent-core complex PIIIC9/AIIF? (3/7 mol mol-1) displayed the widest BPI range of ΔTBPI = 12.0 °C at the correspondent H-acceptor T = PIIIC9 and H-donor D = AIIF?. Since the covalent-bonded bent-core mixture only had narrow ranges of BPIII, we could summarize that the introduction of H-bonds into the bent-core center effectively stabilizes the BPs and easier induces the BPI.

Bioavailable diacylhydrazine ligands for modulating the expression of exogenous genes via an ecdysone receptor complex

The present invention relates to non-steroidal ligands for use in nuclear receptor-based inducible gene expression system, and a method to modulate exogenous gene expression in which an ecdysone receptor complex comprising: a DNA binding domain; a ligand binding domain; a transactivation domain; and a ligand is contacted with a DNA construct comprising: the exogenous gene and a response element; wherein the exogenous gene is under the control of the response element and binding of the DNA binding domain to the response element in the presence of the ligand results in activation or suppression of the gene.

Regio-selective hydroxysubstitution of fluorobenzoic acid derivatives: Facile synthesis of fluorosalicylic acid derivatives

Ortho-substituted fluorine in 2,4-difluorobenzoic acid was found to be regio-selectively replaced to hydroxide by solid sodium hydroxide in 1,3-dimethyl-2-imidazolidinone, to afford 4-fluoro-2-hydroxybenzoic acid in high yield. Several multi-fluoro-substi