2713-31-7

Basic information

• Product Name: 2,5-Difluorophenol
• Synonyms: 2,5-DIFLUOROPHENOL;Phenol,2,5-difluoro-;2,5-Difluorphenol;2,5-Difluorophenol,97%;2,5-Difluorophenol 97%;2,5-Difluorophenol,96%;5-Difluorophenol;1,4-Difluoro-2-hydroxybenzene
• CAS NO: 2713-31-7
• Molecular Formula: C₆H₄F₂O
• Molecular Weight: 130.09
• Product Categories: Fluorobenzene Series;Aromatic Phenols;Phenol&Thiophenol&Mercaptan;Fluorine Compounds;Phenols;Organic Building Blocks;Oxygen Compounds;Aryl Fluorinated Building Blocks;Building Blocks;C6;C6 to C8;Chemical Synthesis;Fluorinated Building Blocks;Organic Building Blocks;Organic Fluorinated Building Blocks;Other Fluorinated Organic Building Blocks;Oxygen Compounds
• Mol File: 2713-31-7.mol
• Article Data: 7

Chemical Properties

• Melting Point: 40-42 °C(lit.)
• Boiling Point: 145 °C
• Flash Point: 128 °F
• Appearance: white crystalline mass
• Density: 1.2483 (estimate)
• Vapor Pressure: 2.16mmHg at 25°C
• Refractive Index: 1.495
• Storage Temp.: Flammables area
• PKA: 7.71±0.10(Predicted)
• Water Solubility: slightly soluble
• BRN: 2081076
• CAS DataBase Reference: 2,5-Difluorophenol(CAS DataBase Reference)
• NIST Chemistry Reference: 2,5-Difluorophenol(2713-31-7)
• EPA Substance Registry System: 2,5-Difluorophenol(2713-31-7)

Safety Data

• Hazard Codes: Xn,Xi,C,F
• Statements: 10-20/21/22-36/37/38-34-11
• Safety Statements: 16-26-36/37-45-36/37/39-36
• RIDADR: UN 1325 4.1/PG 2
• WGK Germany: 3
• HazardClass: 4.1
• PackingGroup: II
• Hazardous Substances Data: 2713-31-7(Hazardous Substances Data)

Usage

Description

2,5-Difluorophenol is a white crystalline mass that is a derivative of phenol, with two fluorine atoms replacing hydrogen atoms at the 2nd and 5th positions on the benzene ring. 2,5-Difluorophenol has unique chemical properties due to the presence of fluorine atoms, which can be utilized in various chemical reactions and applications.

Uses

Used in Pharmaceutical Industry:
2,5-Difluorophenol is used as an intermediate in the synthesis of various pharmaceutical compounds, particularly dior trifluorinated hydroxybenzoic acids. These compounds are valuable in the development of drugs with improved pharmacological properties, such as enhanced bioavailability and increased metabolic stability.
Used in Chemical Synthesis:
2,5-Difluorophenol is used as a starting material for the synthesis of a wide range of organic compounds, including fluorinated aromatics and heterocyclic compounds. The presence of fluorine atoms in the molecule makes it a versatile building block for the creation of new molecules with potential applications in various industries.
Used in Environmental Applications:
The conversion of 2,5-difluorophenol by whole cells of Rhodococcus opacus 1G has been investigated, which suggests that this compound can be utilized in bioremediation processes. The use of microorganisms to convert or degrade harmful chemicals, such as 2,5-difluorophenol, can be an environmentally friendly approach to waste management and pollution control.

InChI:InChI=1/C6H4F2O/c7-4-1-2-5(8)6(9)3-4/h1-3,9H

Synthetic route

2,4,5-trifluorobenzoic acid (446-17-3) → 2,5-difluorophenol (2713-31-7)

Conditions	Yield
With water; sodium hydroxide at 80 - 155℃; for 35h; Sealed tube;	94.1%

para-difluorobenzene (540-36-3) → 2,4-difluorophenol (367-27-1) + 2,5-difluorophenol (2713-31-7)

Conditions	Yield
With dihydrogen peroxide In acetonitrile at 60℃; for 0.416667h;	A 6% B 94%

3-fluorophenol (372-20-3) → 2,5-difluorophenol (2713-31-7)

Conditions	Yield
With acetic acid; Selectfluor; eosin y In water at 20℃; for 6h; Irradiation; Green chemistry;	70%

2,5-difluoroaniline (367-30-6) → 2,5-difluorophenol (2713-31-7)

para-difluorobenzene (540-36-3) → 2,5-difluorophenol (2713-31-7)

Conditions	Yield
Yield given. Multistep reaction;

para-difluorobenzene (540-36-3) → 1,2,4-trifluorobenzene (367-23-7) + 2,5-difluorophenol (2713-31-7) + 4H/5H-3,3,4,5,6,6-Hexafluor-cyclohexen (703-16-2) + 3,3,6,6-tetrafluoro-1,4-cyclohexadiene (22060-77-1)

Conditions	Yield
With trifluorormethanesulfonic acid; fluorine In trichlorofluoromethane at -25℃; for 3h; Further byproducts given. Title compound not separated from byproducts;

ferrous ammonium sulphate + Trimethyl borate (121-43-7) + para-difluorobenzene (540-36-3) → 2,5-difluorophenol (2713-31-7)

Conditions	Yield
With hydrogenchloride; n-butyllithium; dihydrogen peroxide In tetrahydrofuran; hexane; toluene
With hydrogenchloride; n-butyllithium; dihydrogen peroxide In tetrahydrofuran; hexane; toluene

para-difluorobenzene (540-36-3) → 4-Fluorophenol (371-41-5) + 2,4-difluorophenol (367-27-1) + 2,5-difluorophenol (2713-31-7) + hydrogen fluoride (7664-39-3)

Conditions	Yield
With dihydrogen peroxide In acetonitrile at 60℃; for 15h; Catalytic behavior;

2,5-difluorophenol (2713-31-7) + N,N-diethylcarbamyl chloride (88-10-8) → O-2,5-difluorophenyl N,N-diethylcarbamate (1207163-57-2)

Conditions	Yield
With potassium carbonate In acetonitrile at 70℃; for 13.5h;	100%
Stage #1: 2,5-difluorophenol With sodium hydroxide In tetrahydrofuran for 0.166667h; Stage #2: N,N-diethylcarbamyl chloride In tetrahydrofuran at 20℃; for 24h;	92%
Stage #1: 2,5-difluorophenol With sodium hydroxide In tetrahydrofuran at 20℃; for 0.166667h; Stage #2: N,N-diethylcarbamyl chloride In tetrahydrofuran at 20℃; for 24h;
Stage #1: 2,5-difluorophenol With sodium hydroxide In tetrahydrofuran at 20℃; for 0.166667h; Inert atmosphere; Stage #2: N,N-diethylcarbamyl chloride In tetrahydrofuran at 20℃; for 24h; Inert atmosphere;

2,5-difluorophenol (2713-31-7) + 1,1,1,3,3,3-hexamethyl-disilazane (999-97-3) → 1,4-difluoro-2-(trimethylsilyloxy)benzene

Conditions	Yield
at 170℃; for 1h;	99%

2,5-difluorophenol (2713-31-7) + propargyl bromide (106-96-7) → 1,4-difluoro-2-(prop-2-yn-1-yloxy)benzene

Conditions	Yield
Stage #1: 2,5-difluorophenol; propargyl bromide With sodium carbonate In acetone at 60℃; for 8.5h; Stage #2: In acetone at 25℃; for 15h;	99%
With potassium carbonate In acetone for 24h; Inert atmosphere; Reflux;	96.7%
With caesium carbonate In acetonitrile	92%
With potassium carbonate In acetone at 60℃; for 24h; Inert atmosphere;	88%

2,5-difluorophenol (2713-31-7) + tert-butyldimethylsilyl chloride (18162-48-6) → 1-tert-butyldimethylsilyloxy-2,5-difluorobenzene (179420-99-6)

Conditions	Yield
Stage #1: 2,5-difluorophenol With sodium hydride In N,N-dimethyl-formamide for 0.5h; cooling; Stage #2: tert-butyldimethylsilyl chloride In N,N-dimethyl-formamide for 1h;	94%
Stage #1: 2,5-difluorophenol With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 0.5h; Stage #2: tert-butyldimethylsilyl chloride In N,N-dimethyl-formamide at 20℃; for 15h;	80%
In N,N-dimethyl-formamide; mineral oil	26.65 g (94%)

2,5-difluorophenol (2713-31-7) + aniline (62-53-3) → 2,5-difluoro-4-phenylazophenol (847872-05-3)

Conditions	Yield
Stage #1: aniline With hydrogenchloride; sodium nitrite In water at 0 - 5℃; Stage #2: 2,5-difluorophenol With sodium hydroxide In water Stage #3: With hydrogenchloride more than 3 stages;	93%
Stage #1: aniline With hydrogenchloride; sodium nitrite In water Stage #2: 2,5-difluorophenol With sodium hydroxide; urea In water at 0 - 20℃;	74%

N-(2-nitro-5-chlorophenyl)-N-methylcarbamic acid t-butyl ester (299176-17-3) + 2,5-difluorophenol (2713-31-7) → tert-butyl [5-(2,5-difluorophenoxy)-2-nitrophenyl]methylcarbamate (1072003-46-3)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 80℃; for 10h; Inert atmosphere;	92%

formaldehyd (50-00-0) + 2,5-difluorophenol (2713-31-7) → 3,6-difluoro-2-(hydroxymethyl)phenol (1244949-79-8)

Conditions	Yield
With sodium metaborate tetrahydrate In water at 40℃; for 12h; Green chemistry; regioselective reaction;	92%

2,5-difluorophenol (2713-31-7) + 3,4-bis(4-methoxyphenyl)-6-chloropyridazine (67820-94-4) → 3,4-bis(4-methoxyphenyl)-6-(2,5-difluorophenoxy)pyridazine

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 150℃; for 24h;	91.5%
at 150℃; for 24h;	91.5%

2,5-difluorophenol (2713-31-7) + chloromethyl methyl ether (107-30-2) → 1,4-difluoro-2-(methoxymethoxy)benzene (749230-16-8)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 25℃; for 2h;	91%
Stage #1: 2,5-difluorophenol With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.5h; Inert atmosphere; Stage #2: chloromethyl methyl ether In dichloromethane at 20℃; for 16h;	77.97%

2,5-difluorophenol (2713-31-7) + (S)-3-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester (101469-92-5) → tert-butyl (R)-3-(2,5-difluorophenoxy)pyrrolidine-1-carboxylate

Conditions	Yield
Stage #1: 2,5-difluorophenol; (S)-3-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester In tetrahydrofuran at 20℃; for 0.166667h; Stage #2: With di-tert-butyl-diazodicarboxylate In tetrahydrofuran at 20℃;	90%

2,5-difluorophenol (2713-31-7) + dimethyl sulfate (77-78-1) → 2,5-difluoroanisole (75626-17-4)

Conditions	Yield
With potassium carbonate In acetone for 2h; Heating;	89%
With potassium carbonate In acetone for 2h; Reflux;	81.4%

2,5-difluorophenol (2713-31-7) + 1-(2-methoxyphenyl)-1H-pyrazol (102908-37-2) → 1-(2',5'-difluoro-3-methoxybiphenyl-2-yl)-1H-pyrazole (1373210-92-4)

Conditions	Yield
With [Ru(MesCO2)2(p-cymene)]; potassium carbonate; p-toluenesulfonyl chloride In toluene at 120℃; for 18h; Inert atmosphere; chemoselective reaction;	89%

2,5-difluorophenol (2713-31-7) + (hex-1-en-3-yl)methyl carbonate (83135-00-6) → (R)-1,4-difluoro-2-(hex-1-en-3-yloxy)benzene

Conditions	Yield
With (R,R)-(−)-2,3-bis(t-butylmethylphosphino)quinoxaline; chloro(1,5-cyclooctadiene)rhodium(I) dimer In dichloromethane at 20℃; for 24h; Schlenk technique; Inert atmosphere; Sealed tube; enantioselective reaction;	88%

2,5-difluorophenol (2713-31-7) → 2-bromo-3,6-difluoro phenol (1208077-18-2)

Conditions	Yield
With N-Bromosuccinimide In tetrahydrofuran at -40℃; for 2h;	85.3%
With N-Bromosuccinimide In tetrahydrofuran at -40 - 20℃; for 1h;	57%
With N-Bromosuccinimide; isopropylamine In tetrahydrofuran at -40 - 20℃; for 0.5h;	51%

2,5-difluorophenol (2713-31-7) + benzyl bromide (100-39-0) → 1-(benzyloxy)-2,5-difluorobenzene (152434-79-2)

Conditions	Yield
With potassium carbonate In acetone Heating;	84%

trifluoromethylsulfonic anhydride (358-23-6) + 2,5-difluorophenol (2713-31-7) → Trifluoro-methanesulfonic acid 2,5-difluoro-phenyl ester (211512-93-5)

Conditions	Yield
With pyridine In dichloromethane for 4h; Ambient temperature;	84%

formaldehyd (50-00-0) + 2,5-difluorophenol (2713-31-7) → C13H8F4O2

Conditions	Yield
With phosphoric acid In toluene at 90℃; for 20h;	82%

2,5-difluorophenol (2713-31-7) → 4-bromo-2,5-difluoro phenol (486424-36-6)

Conditions	Yield
With bromine In chloroform at 0 - 20℃; for 3h;	81.05%
With bromine In chloroform for 3h;	70.2%
With bromine In chloroform for 3h;	70.2%
With bromine; trifluoroacetic acid at 20℃;

2,5-difluorophenol (2713-31-7) + 4-Fluoronitrobenzene (350-46-9) → 1,4-difluoro-2-(4-nitrophenoxy)benzene (1414356-66-3)

Conditions	Yield
Stage #1: 4-Fluoronitrobenzene With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 25℃; for 2.33333h; Inert atmosphere; Stage #2: 2,5-difluorophenol With copper(l) chloride In N,N-dimethyl-formamide; mineral oil at 100℃; for 12h;	81%
Stage #1: 4-Fluoronitrobenzene With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 25℃; for 2.33333h; Inert atmosphere; Stage #2: 2,5-difluorophenol; copper(l) chloride In N,N-dimethyl-formamide; mineral oil at 25 - 100℃; for 12.1667h;	81%
Stage #1: 4-Fluoronitrobenzene With sodium hydride In N,N-dimethyl-formamide at 0 - 25℃; for 2.33333h; Stage #2: 2,5-difluorophenol With copper(l) chloride In N,N-dimethyl-formamide at 25 - 100℃; for 12h;	81%
Stage #1: 4-Fluoronitrobenzene With sodium hydride In N,N-dimethyl-formamide at 0 - 25℃; for 2.33h; Stage #2: 2,5-difluorophenol With copper(l) chloride In N,N-dimethyl-formamide at 25 - 100℃; for 12.13h;	81%
Stage #1: 4-Fluoronitrobenzene With sodium hydride In N,N-dimethyl-formamide at 0 - 25℃; for 2.33333h; Stage #2: 2,5-difluorophenol With copper(l) chloride In dichloromethane at 25 - 100℃; for 12h;	81%

2,5-difluorophenol (2713-31-7) + propargyl bromide (106-96-7) → 2,4-difluoro-1-(prop-2-yn-1-yloxy)benzene (672946-37-1)

Conditions	Yield
With potassium carbonate In acetone Heating / reflux;	80%

2,5-difluorophenol (2713-31-7) + para-methylphenylmagnesium bromide (4294-57-9) → 4-fluoro-4'-methylbiphenyl-2-ol

Conditions	Yield
With (bis(tricyclohexyl)phosphine)palladium(II) dichloride In tetrahydrofuran at 50℃; for 24h; Inert atmosphere;	79%
With (bis(tricyclohexyl)phosphine)palladium(II) dichloride In tetrahydrofuran at 50℃; for 24h;	79%

4-[4-(3-hydroxypropyl)phenyl]-5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (642487-34-1) + 2,5-difluorophenol (2713-31-7) → 4-{4-[3-(2,5-difluorophenoxy)propyl]phenyl}-5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (642487-38-5)

Conditions	Yield
With tributylphosphine; N-ethyl-N,N-diisopropylamine; 1,1'-azodicarbonyl-dipiperidine In toluene at 20 - 60℃; for 3h;	77%

6-(4-hydroxypiperidin-1-yl)-N-isopentylpyridazine-3-carboxamide (944808-07-5) + 2,5-difluorophenol (2713-31-7) → C21H26F2N4O2

Conditions	Yield
With di-tert-butyl-diazodicarboxylate; triphenylphosphine In tetrahydrofuran at 25℃; for 0.5h; Mitsunobu reaction;	70%

2,5-difluorophenol (2713-31-7) → 2,4,5-tribromo-3,6-difluorophenol

Conditions	Yield
With bromine; iron In various solvent(s) Heating;	66.3%

Ethyl 2-butynoate (4341-76-8) + 2,5-difluorophenol (2713-31-7) → 3-(2,5-difluoro-phenoxy)-but-2-enoic acid ethyl ester (1191998-38-5)

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran at 130℃; for 2h;	63%

2,5-difluorophenol (2713-31-7) + cis-3-hydroxycyclobutylcarboxylic acid methyl ester (63485-50-7) → (trans)-methyl 3-(2,5-difluorophenoxy)cyclobutanecarboxylate

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0 - 20℃; for 72h;	63%

4-chloro-3-iodopyridin-2-ylamine (417721-69-8) + 2,5-difluorophenol (2713-31-7) → 4-(2,5-difluorophenoxy)-3-iodopyridin-2-amine (1345854-91-2)

Conditions	Yield
Stage #1: 4-chloro-3-iodopyridin-2-ylamine; 2,5-difluorophenol With 1,8-diazabicyclo[5.4.0]undec-7-ene In 1-methyl-pyrrolidin-2-one at 170℃; for 6h; Microwave irradiation; Stage #2: With sodium hydroxide In 1-methyl-pyrrolidin-2-one; water	62.1%

Upstream product

• 367-30-6 2,5-difluoroaniline 
• 540-36-3 para-difluorobenzene 
• 121-43-7 Trimethyl borate 
• 372-20-3 3-fluorophenol 
• 446-17-3 2,4,5-trifluorobenzoic acid 

Downstream Products

• 366-56-3 (2,5-difluoro-phenoxy)-acetic acid 
• 139548-97-3 2,5-difluoro-6-nitrophenol 
• 152434-79-2 1-(benzyloxy)-2,5-difluorobenzene 
• 75626-17-4 2,5-difluoroanisole 
• 211512-93-5 Trifluoro-methanesulfonic acid 2,5-difluoro-phenyl ester 
• 182756-52-1 2,5-difluorotyrosine 
• 211501-32-5 (R)-2-[2-(2,5-difluorophenoxy)-1-methylethyl]-1H-isoindole-1,3(2H)-dione 
• 741667-82-3 (1S,2R)-1-(2,5-difluorophenoxy)-1-phenylprop-2-ylamine 
• 196519-69-4 2-allyloxy-1,4-difluoro-benzene 
• 749230-16-8 1,4-difluoro-2-(methoxymethoxy)benzene 
• 847872-05-3 2,5-difluoro-4-phenylazophenol 
• 486424-36-6 4-bromo-2,5-difluoro phenol 
• 179420-99-6 1-tert-butyldimethylsilyloxy-2,5-difluorobenzene 
• 919355-35-4 2,5-difluoro-3-hydroxyphenylboronic acid 

Relevant articles and documents

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Cephalosporins

A syn isomer in (R) or (S) form or a mixture thereof of a compound of the formula STR1 syn isomer, in the (R) or (S) form or in the form of an (R,S) mixture, in the form of an internal salt or their salts with organic or mineral acids, wherein the variables are herein below defined, having antibacterial properties.