65145-13-3

Usage

Uses

Used in Pharmaceutical Industry:
2-Fluoro-4-hydroxybenzoic acid is used as a key intermediate in the synthesis of various pharmaceuticals for its ability to enhance the properties of the final drug products. Its incorporation into drug molecules can improve their stability, solubility, and bioavailability, leading to more effective treatments.
Used in Antioxidant Applications:
2-Fluoro-4-hydroxybenzoic acid is used as an antioxidant in various applications, including the food, cosmetic, and pharmaceutical industries. Its antioxidant activity helps to protect against oxidative stress and damage, which can be beneficial in maintaining the quality and shelf life of products.
Used in Bioactive Compounds Synthesis:
2-Fluoro-4-hydroxybenzoic acid is used as a building block in the synthesis of complex biologically active compounds. Its unique structure allows for the development of new molecules with potential therapeutic applications, such as antimicrobial, antiviral, and anticancer agents.

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 
• 203115-96-2 2-fluoro-4-propoxybenzoic acid 
• 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 
• 331-64-6 2-fluoro-4-methoxy-benzaldehyde 
• 394-42-3 2-fluoro-4-methoxy-benzoic acid 
• 217978-01-3 ethyl-2-fluoro-4-hydroxy-benzoate 
• 126940-10-1 1-fluoro-3-(methoxy-methoxy)benzene 
• 860296-15-7 3-chloro-2-fluoro-4-hydroxybenzoic acid 
• 860296-13-5 2-chloro-1-fluoro-3-(methoxymethoxy)benzene 
• 121219-03-2 4-bromo-3-fluorophenol 
• 372-20-3 3-fluorophenol 

Downstream Products

• 128895-75-0 4-n-hexyloxy-2-fluorobenzoic acid 
• 119810-26-3 2-Fluoro-4-hydroxy-benzoic acid 2-methyl-butyl ester 
• 96740-92-0 3-fluoro-4-(hydroxymethyl)phenol 
• 521074-57-7 2-fluoro-4-(4-fluorobutoxy)benzoic acid 
• 136386-10-2 2-fluoro-4-n-tridecanoyloxybenzoic acid 
• 911135-12-1 3-chloropropyl 4-(3-chloropropoxy)-2-fluorobenzoate 
• 114045-96-4 4-Benzyloxy-2-fluoro-benzoic Acid 
• 106315-86-0 (S)-(+)-2-methylbutyl 4-hydroxy-2-fluorobenzoate 
• 1205681-06-6 biphenyl-2-yl-carbamic acid 1-(2-{4-[2-(2-fluoro-4-hydroxy-benzoylamino)-ethyl]-phenyl}-ethyl)-piperidin-4-yl ester 
• 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 

Relevant academic research and scientific papers

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.

Synthesis of fluorosubstituted three ring esters and their dielectric properties

Laterally substituted by fluorine atoms 4-cyanophenyl 4-(4- pentylbenzoyloxy)-benzoates have been prepared and their phase transition temperatures, enthalpies and dielectric properties upon frequency were evaluated. The novel compounds exhibit a broad range of nematic mesophase, large positive dielectric anisotropy changing sign at low frequency. They are convenient components of LC mixtures for dual frequency addressing devices. Copyright Taylor & Francis Group, LLC.

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.

Converting core compounds into building blocks: The concept of regiochemically exhaustive functionalization

In a model study, 3-fluorophenol and 3-fluoropyridine were converted into the each time four possible carboxylic acids by passing through the corresponding organometallic intermediates. As an attempt to generalize the findings reveals, a restricted set of principles and methods suffices to cope with all standard scenarios. The most valuable and versatile tools for the regiochemically exhaustive functionalization of a great variety of substrate patterns are the optionally site-selective metalation (either by reagent/substrate matching or by peripheral coordination control), the use of activating or congesting protective groups and the basicity gradient-driven heavy halogen migration (followed by halogen/metal permutation). Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005.

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

Compounds having activity as inhibitors of cytochrome P450RAI

Compounds having Formula 2 wherein the symbols have the meaning defined in the specification are inhibitors of the cytochrome P450RAI (retinoic acid inducible) enzyme, and are used for treating diseases responsive to treatment by retinoids.

Benzopyran derivatives having leukotriene-antagonistic action

The present invention relates to novel 4-oxo-4H-1-benzopyran compounds containing benzyloxymethyl, 3-phenylpropyl, or other araliphatic substituents in their 8-position. These compounds show a leukotriene-antagonistic activity. The compounds are characterized by good oral adsorption. The compounds of the present invention may be used as anti-inflammatory and antiallergic medicaments, and in the treatment of cardiovascular diseases.

Liquid crystal materials, mixtures and devices

Liquid crystal compounds of formula I may be used by themselves or they may be mixed with other liquid crystal compounds to give useful liquid crystal mixtures which may then be used in liquid crystal devices. The materials exhibit smectic mesophases and may therefore be used in ferroelectric, ferrielectric, antiferroelectric, themochromic and electroclinic devices. They may also be used as long pitch materials.

Fluorinated linkers for monitoring solid-phase synthesis using gel- phase 19F NMR spectroscopy

Three fluorinated linkers which are analogues of linkers commonly used in solid-phase peptide synthesis have been prepared. Using 19F NMR spectroscopy, the fluorine atom of the linker allowed monitoring of several transformations in the solid-phase synthesis of a peptoid having a coumarin moiety. Especially, attachment of the linker to the solid phase, coupling of the first building block to the linker and cleavage of the product were efficiently monitored and optimised.

The Synthesis and Liquid Crystal Properties of Some Laterally Fluorinated trans-Cyclohexane-1-carboxylate and Benzoate Esters

A large number of laterally fluorinated 4-n-alkyl- and -alkoxy-phenyl 4'-n-alkyl- and -alkoxy-bezoates and 4-n-alkylphenyl trans-4'-n-alkyl- and -alkoxy-cyclohexane-1-carboxylates were synthesised.In these compounds, the lateral fluoro-substituent was situated in either the phenol or the carboxylic acid moiety of the molecules for the benzoate esters, but only in the phenol moiety for the trans-cyclohexane-1-carboxylate esters.The nematic thermal stabilities for the fluorophenyl bezoate and trans-cyclohexane-1-carboxylate esters and the fluorobenzoate esters were compared with those for the corresponding non-fluorinated analogues.A nematic thermal efficiency order was derived for the 4-n-alkyl-fluorophenyl 4-n-alkylbezoate and trans-4-n-alkylcyclohexane-1-carboxylate esters, but only in the case of the latter esters, which were extensively examined, was the smectic tendency of the system investigated.Explanations are given for the observed nematic and smectic thermal stabilities of the titled esters, and some of their physical properties are discussed.