461-96-1

Basic information

• Product Name: 1-Bromo-3,5-difluorobenzene
• Synonyms: 1-BROMO-3,5-DIFLUOROBENZENE;3,5-DIFLUOROBROMOBENZENE;1-Bromo-3,5-difluorobenzene,98% [3,5-Difluorobromobenzene];3,5-difluoro-1-bromobenzene;1-Bromo-3,5-difluorobenzene 98%;1-Bromo-3,5-difluorobenzene98%;1-Brom-3,5-difluorbenzol;3,5-DIFLUOROBROMOBENZENE A.K.A.1-BROMO-3,5-DIFLUOR
• CAS NO: 461-96-1
• Molecular Formula: C₆H₃BrF₂
• Molecular Weight: 192.99
• EINECS: 416-710-2
• Product Categories: Aromatic Hydrocarbons (substituted) & Derivatives;Fluorobenzene;Miscellaneous;Aryl;C6;Halogenated Hydrocarbons;Fluorine series
• Mol File: 461-96-1.mol
• Article Data: 11

Chemical Properties

• Melting Point: -27 °C
• Boiling Point: 140 °C(lit.)
• Flash Point: 112 °F
• Appearance: Clear colorless to light yellow/Liquid
• Density: 1.676 g/mL at 25 °C(lit.)
• Vapor Pressure: 7.81mmHg at 25°C
• Refractive Index: n20/D 1.499(lit.)
• Storage Temp.: Flammables area
• Solubility: 0.238g/l
• Water Solubility: 0.238 g/L (20 ºC)
• BRN: 1931520
• CAS DataBase Reference: 1-Bromo-3,5-difluorobenzene(CAS DataBase Reference)
• NIST Chemistry Reference: 1-Bromo-3,5-difluorobenzene(461-96-1)
• EPA Substance Registry System: 1-Bromo-3,5-difluorobenzene(461-96-1)

Safety Data

• Hazard Codes: Xn,N,F,Xi
• Statements: 10-22-38-43-48/22-50/53-36/37/38
• Safety Statements: 24-36/37-60-61-36-26-16
• RIDADR: UN 1993 3/PG 3
• WGK Germany: 2
• HazardClass: 3
• PackingGroup: III
• Hazardous Substances Data: 461-96-1(Hazardous Substances Data)

Usage

Chemical Properties

CLEAR COLOURLESS TO LIGHT YELLOW LIQUID

Uses

Different sources of media describe the Uses of 461-96-1 differently. You can refer to the following data:
1. Intermediates of Liquid Crystals
2. 1-Bromo-3,5-difluorobenzene was used in the synthesis of 4-bromo-2,6-difluorobenzoic acid.

Synthesis Reference(s)

Journal of Medicinal Chemistry, 30, p. 486, 1987 DOI: 10.1021/jm00386a008

InChI:InChI=1/C6H3BrF2/c7-4-1-5(8)3-6(9)2-4/h1-3H

Synthetic route

(4-bromo-2,6-difluorophenyl)triethylsilane (184910-37-0) → 3,5-difluorobromobenzene (461-96-1)

Conditions	Yield
With potassium fluoride In tetrahydrofuran; water for 2h; Heating;	93%

hypophosphorous acid (6303-21-5) + 2-bromo-4,6-difluoroaniline hydrobromide (101471-20-9) → 3,5-difluorobromobenzene (461-96-1)

Conditions	Yield
With sodium nitrite In hydrogenchloride	75%

1,3-dibromo-5-fluorobenzene (1435-51-4) → 3,5-difluorobromobenzene (461-96-1)

Conditions	Yield
Stage #1: 1,3-dibromo-5-fluorobenzene With TurboGrignard In tetrahydrofuran; 1,4-dioxane at 0 - 25℃; Inert atmosphere; Stage #2: With N-fluorobis(benzenesulfon)imide In dichloromethane; octadecafluorodecahydronaphthalene (cis+trans) at -78 - 20℃; Inert atmosphere;	66%
Stage #1: 1,3-dibromo-5-fluorobenzene With TurboGrignard In tetrahydrofuran at 25℃; Inert atmosphere; Stage #2: With N-fluorobis(benzenesulfon)imide In dichloromethane; octadecafluorodecahydronaphthalene (cis+trans) at -78 - 25℃; Inert atmosphere;	66 %Chromat.

2-Brom-4,6-difluor-benzoldiazonium-chlorid → 3,5-difluorobromobenzene (461-96-1)

Conditions	Yield
With hypophosphoric acid

1,3-Difluorobenzene (372-18-9) → 3,5-difluorobromobenzene (461-96-1) + 1,4 - dibromo-2,6-difluorobenzene (128259-71-2) + 1,3-Difluoro-1,2,3,4,5,6-hexabromocyclohexane (128259-73-4) + 2,4,5-Tribromo-1,3-difluorobenzene (128259-72-3)

Conditions	Yield
With bromine In trichlorofluoromethane Irradiation; Further byproducts given. Yields of byproduct given;	A n/a B n/a C 2.01 g D n/a

2-bromo-4,6-difluoroaniline hydrobromide (101471-20-9) → 3,5-difluorobromobenzene (461-96-1)

Conditions	Yield
With sodium hypophosphite; hydrogen bromide; sodium nitrite Yield given. Multistep reaction;
With hydrogenchloride; hypophosphorous acid; sodium nitrite 1.) water, 5 deg C, 2.) water, 0 deg C, 3 h; Yield given. Multistep reaction;

3,5-difluoroaniline (372-39-4) → 3,5-difluorobromobenzene (461-96-1)

Conditions	Yield
Substitution; Sandmeyer reaction;

1,3-Difluorobenzene (372-18-9) → 3,5-difluorobromobenzene (461-96-1)

Conditions

Yield

Multi-step reaction with 6 steps 1: 89 percent / butyllithium / hexane; tetrahydrofuran / -75 °C 2: 92 percent / sec-butyllithium; bromine / cyclohexane; tetrahydrofuran / 0.75 h 3: 82 percent / diisopropylamine; butyllithium / hexane; tetrahydrofuran / -75 °C 4: diisopropylamine; butyllithium / hexane; tetrahydrofuran / 2 h / -75 °C 5: 59 percent / butyllithium / diethyl ether; hexane / 0.25 h / -100 °C 6: 93 percent / potassium fluoride / tetrahydrofuran; H2O / 2 h / Heating View Scheme

1-triethylsilyl-2,6-difluorobenzene (651027-02-0) → 3,5-difluorobromobenzene (461-96-1)

Conditions

Yield

Multi-step reaction with 5 steps 1: 92 percent / sec-butyllithium; bromine / cyclohexane; tetrahydrofuran / 0.75 h 2: 82 percent / diisopropylamine; butyllithium / hexane; tetrahydrofuran / -75 °C 3: diisopropylamine; butyllithium / hexane; tetrahydrofuran / 2 h / -75 °C 4: 59 percent / butyllithium / diethyl ether; hexane / 0.25 h / -100 °C 5: 93 percent / potassium fluoride / tetrahydrofuran; H2O / 2 h / Heating View Scheme

(3-bromo-2,6-difluorophenyl)triethylsilane (651027-03-1) → 3,5-difluorobromobenzene (461-96-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: 82 percent / diisopropylamine; butyllithium / hexane; tetrahydrofuran / -75 °C 2: diisopropylamine; butyllithium / hexane; tetrahydrofuran / 2 h / -75 °C 3: 59 percent / butyllithium / diethyl ether; hexane / 0.25 h / -100 °C 4: 93 percent / potassium fluoride / tetrahydrofuran; H2O / 2 h / Heating View Scheme

(3,4-dibromo-2,6-difluorophenyl)triethylsilane (651027-05-3) → 3,5-difluorobromobenzene (461-96-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 59 percent / butyllithium / diethyl ether; hexane / 0.25 h / -100 °C 2: 93 percent / potassium fluoride / tetrahydrofuran; H2O / 2 h / Heating View Scheme

(3,5-dibromo-2,6-difluorophenyl)triethylsilane (651027-04-2) → 3,5-difluorobromobenzene (461-96-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: diisopropylamine; butyllithium / hexane; tetrahydrofuran / 2 h / -75 °C 2: 59 percent / butyllithium / diethyl ether; hexane / 0.25 h / -100 °C 3: 93 percent / potassium fluoride / tetrahydrofuran; H2O / 2 h / Heating View Scheme

2,4-difluorophenylamine (367-25-9) → 3,5-difluorobromobenzene (461-96-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 91 percent / Br2 / acetic acid / 0.25 h / Ambient temperature 2: 1.) 12 N HCl, NaNO2, 2.) 50 percent H3PO2 / 1.) water, 5 deg C, 2.) water, 0 deg C, 3 h View Scheme
Multi-step reaction with 2 steps 1: 88 percent / Br2, acetic acid 2: 1.) NaNO2, HBr, 2.) NaH2PO2*xH2O View Scheme

2-bromo-4,6-difluoroaniline (444-14-4) + copper(I) oxide (1317-39-1, 146060-06-2) → 3,5-difluorobromobenzene (461-96-1)

Conditions	Yield
With ammonium hydroxide

2-bromo-4,6-difluoroaniline hydrochloride → 3,5-difluorobromobenzene (461-96-1)

Conditions	Yield
Stage #1: 2-bromo-4,6-difluoroaniline hydrochloride With sodium nitrite In water at 0 - 5℃; for 1h; Green chemistry; Stage #2: With sodium hypophosphite In water for 2h; Green chemistry;	190.9 g

chloro-trimethyl-silane (75-77-4) + 3,5-difluorobromobenzene (461-96-1) → (4-bromo-2,6-difluoro-phenyl)-trimethyl-silane (184910-20-1)

Conditions	Yield
Stage #1: 3,5-difluorobromobenzene With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -100 - -90℃; for 2h; Stage #2: chloro-trimethyl-silane In tetrahydrofuran; hexane at -85℃;	100%
Stage #1: 3,5-difluorobromobenzene With n-butyllithium; diisopropylamine In tetrahydrofuran at -100 - -90℃; for 2.33333h; Stage #2: chloro-trimethyl-silane In tetrahydrofuran at -100 - 20℃;	100%
With n-butyllithium In tetrahydrofuran; hexane at -75℃;	93%
Stage #1: 3,5-difluorobromobenzene With n-butyllithium; diisopropylamine In tetrahydrofuran at -100℃; for 2h; Stage #2: chloro-trimethyl-silane In tetrahydrofuran at -100 - 20℃; for 16h;

3,5-difluorobromobenzene (461-96-1) + 1-t-Butoxycarbonylpiperazine (57260-71-6) → tert-butyl 4-(3,5-difluorophenyl)piperazine-1-carboxylate (909418-94-6)

Conditions	Yield
Stage #1: 3,5-difluorobromobenzene; 1-t-Butoxycarbonylpiperazine With tri-tert-butyl phosphine; palladium diacetate; sodium t-butanolate In xylene at 50℃; Stage #2: With macroporous polymer-supported isocyanate In xylene at 50℃; for 24h;	100%
With tris-(dibenzylideneacetone)dipalladium(0); johnphos; sodium t-butanolate In toluene for 15h; Inert atmosphere; Reflux;	100%
With tris-(dibenzylideneacetone)dipalladium(0); johnphos; sodium t-butanolate In toluene for 15.5h; Time; Inert atmosphere; Reflux;	100%
With Quinuclidine; nickel(II) bromide trihydrate In N,N-dimethyl acetamide at 20℃; for 3h; Sealed tube; Irradiation; Inert atmosphere;	62%

3,5-difluorobromobenzene (461-96-1) + cyclohexylmagnesium bromide (931-50-0) → 1-cyclohexyl-3,5-difluorobenzene

Conditions	Yield
Stage #1: 3,5-difluorobromobenzene With dichloro [1,1'-bis(diphenylphosphino)propane]palladium(II) In tetrahydrofuran for 0.0833333h; Suzuki-Miyaura Coupling; Inert atmosphere; Schlenk technique; Stage #2: cyclohexylmagnesium bromide With lithium bromide In tetrahydrofuran at 20℃; for 24h; Reagent/catalyst; Inert atmosphere; Schlenk technique;	100%

trifluoroethylamine (753-90-2) + 3,5-difluorobromobenzene (461-96-1) → 3,5-difluoro-N-(2,2,2-trifluoroethyl)aniline

Conditions	Yield
With bis(η3-allyl-μ-chloropalladium(II)); 5-(di(adamantan-1-yl)phosphino)-1′,3′,5′-triphenyl-1′H-1,4′-bipyrazole; potassium phenolate In 1,4-dioxane at 100℃; for 6h; Sealed tube; Inert atmosphere;	100%

3,5-difluorobromobenzene (461-96-1) + bis(pinacol)diborane (73183-34-3) → 2-(4-bromo-2,6-difluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Conditions	Yield
With bis(1,5-cyclooctadiene)diiridium(I) dichloride; 1-(4,4'-di-tert-butyl-[2,2'-bipyridin]-6-yl)-2-(dimethyl(phenyl)silyl)-2,3-dihydro-1H-benzo[d][1,3,2]diazaborole at 140℃; for 12h; Inert atmosphere; Schlenk technique; Sealed tube;	99%
With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; cyclopentyl methyl ether; 1,1'-di(pyridin-2-yl)-1,1',3,3'-tetrahydro-2,2'-bibenzo[d][1,3,2]diazaborole at 100℃; for 16h; Schlenk technique; Inert atmosphere;	87%
With (1,5-cyclooctadiene)(methoxy)iridium(l) dimer; 4,4'-di-tert-butyl-2,2'-bipyridine In tetrahydrofuran at 80℃; for 24h; Inert atmosphere;

sodium 2'‐(dicyclohexylphosphaneyl)‐2,6‐diisopropyl‐[1,1'‐biphenyl]‐3‐sulfonate + bis[(trimethylsilyl)methyl](1,5-cyclooctadiene)palladium(II) (225931-80-6) + 3,5-difluorobromobenzene (461-96-1) → C32H37BrF2O5PPdS(1-)*Na(1+)

Conditions	Yield
In tetrahydrofuran at 20℃; for 1h;	99%

3,5-difluorobromobenzene (461-96-1) + ethyl 6-benzyl-2,6-diazaspiro[3.4]octane-8-carboxylate → ethyl 7-benzyl-2-(3,5-difluorophenyl)-2,7-diazaspiro[3.4]octane-5-carboxylate

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; ruphos In tert-butyl alcohol at 110℃; Buchwald-Hartwig Coupling; Inert atmosphere; Sealed tube;	99%

3,5-difluorobromobenzene (461-96-1) + benzyl alcohol (100-51-6) → 5-benzyloxy-3-fluorophenyl bromide (130722-44-0)

Conditions	Yield
Stage #1: benzyl alcohol With sodium hydride In tetrahydrofuran for 1h; Stage #2: 3,5-difluorobromobenzene In tetrahydrofuran at 20℃; for 49h;	98%
Stage #1: benzyl alcohol With sodium hydride In tetrahydrofuran for 1h; Stage #2: 3,5-difluorobromobenzene In tetrahydrofuran at 20℃; for 49h;	98%
Stage #1: benzyl alcohol With sodium hydride In tetrahydrofuran; mineral oil for 1h; Stage #2: 3,5-difluorobromobenzene In tetrahydrofuran; mineral oil at 20 - 40℃;	82%

3,5-difluorobromobenzene (461-96-1) + 4-cyclobutenylbenzeneboronic acid → 4'-cyclobutenyl-3,5-difluorobiphenyl

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); tetrabutylammomium bromide; potassium carbonate In ethanol; water at 40 - 72℃; for 4h; Inert atmosphere;	98%

3,5-difluorobromobenzene (461-96-1) + 4-cyclopentenylbenzeneboronic acid → 4'-cyclopentenyl-3,5-difluorobiphenyl

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); tetrabutylammomium bromide; potassium carbonate In ethanol; water at 40 - 72℃; Inert atmosphere;	98%

3,5-difluorobromobenzene (461-96-1) + [4-(cycloprop-1-en-1-yl)phenyl]boronic acid → 4'-cyclopropenyl-3,5-difluorobiphenyl

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); tetrabutylammomium bromide; potassium carbonate In ethanol; water at 40 - 72℃; for 4h; Inert atmosphere;	98%

3,5-difluorobromobenzene (461-96-1) → 1,3-Difluorobenzene (372-18-9)

Conditions	Yield
With potassium carbonate; butan-1-ol; palladium diacetate; triphenylphosphine at 100℃; for 1h;	97%
With N,N,N,N,-tetramethylethylenediamine; C41H40IrN6 In acetonitrile at 45℃; for 48h; Sealed tube; Glovebox; Inert atmosphere;	52%
With 1,3-dimethyl-2-phenyl-2,3-dihydro-1H-benzo[d]imidazole; C39H45IrN4 In N,N-dimethyl-formamide at 45℃; for 24h; Reagent/catalyst; Irradiation; Glovebox;	97 %Spectr.

carbon dioxide (124-38-9) + 3,5-difluorobromobenzene (461-96-1) → 4-bromo-2,6-difluorobenzoic acid (183065-68-1)

Conditions	Yield
With 2,2,6,6-tetramethyl-piperidine; n-butyllithium In tetrahydrofuran; hexane at -75℃; for 2h;	96%
Stage #1: 3,5-difluorobromobenzene With lithium diisopropyl amide In tetrahydrofuran; hexane at -78℃; for 2h; Stage #2: carbon dioxide In tetrahydrofuran; hexane at -78℃; under 150.012 Torr; for 0.5h;	86.8%
Stage #1: 3,5-difluorobromobenzene With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78℃; for 1.75h; Stage #2: carbon dioxide at 20℃; for 16h;	84%

3,5-difluorobromobenzene (461-96-1) → [2-(3,5-difluorophenyl)ethynyl]trimethylsilane (445491-09-8)

Conditions	Yield
	96%

3,5-difluorobromobenzene (461-96-1) + ethyl 2-(dimethyl(oxo)-λ6-sulfaneylidene)acetate (19956-89-9) → C12H14F2O3S

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); caesium carbonate In acetonitrile at 80℃; for 15h; Inert atmosphere; Schlenk technique; Sealed tube;	96%

3,5-difluorobromobenzene (461-96-1) + 2-(3-fluoro-4-trimethylsilylphenyl)-5,5-dimethyl[1,3,2]dioxaborinane (574755-29-6) → 3,3',5'-trifluoro-4-trimethylsilylbiphenyl (574755-48-9)

Conditions	Yield
With potassium carbonate; tetrakis(triphenylphosphine) palladium(0) In 1,4-dioxane Suzuki coupling; Heating;	95%

3,5-difluorobromobenzene (461-96-1) + para-methylphenylmagnesium bromide (4294-57-9) → 3,5-difluoro-4'-methyl-1,1'-biphenyl

Conditions	Yield
With nickel(II) fluoride; 1,3-bis[2,6-diisopropylphenyl]imidazolium chloride In tetrahydrofuran at 0 - 40℃; for 18.5h; Inert atmosphere;	95%

3,5-difluorobromobenzene (461-96-1) + 2-[2-(trimethylsilyl)ethynyl]benzaldehyde (77123-58-1) → (3,5-difluorophenyl)(2-((trimethylsilyl)ethynyl)phenyl)methanol (1638754-71-8)

Conditions	Yield
Stage #1: 3,5-difluorobromobenzene With iodine; magnesium Stage #2: 2-[2-(trimethylsilyl)ethynyl]benzaldehyde In tetrahydrofuran at -78 - 20℃; for 1h;	95%

3,5-difluorobromobenzene (461-96-1) + 2-hydroxy-2-methylpropanenitrile (75-86-5) → 3,5-difluorobenzonitrile (64248-63-1)

Conditions	Yield
Stage #1: 3,5-difluorobromobenzene With copper(l) iodide; 1,10-Phenanthroline; potassium iodide In N,N-dimethyl-formamide at 110℃; for 6h; Stage #2: 2-hydroxy-2-methylpropanenitrile With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 110℃; for 60h;	94%

3,5-difluorobromobenzene (461-96-1) → 3-bromo-5-fluorophenol (433939-27-6)

Conditions	Yield
Stage #1: 3,5-difluorobromobenzene With 2-(methylsulfonyl)ethyl alcohol; potassium tert-butylate In dimethyl sulfoxide at 0 - 20℃; for 3h; Stage #2: With hydrogenchloride In water; dimethyl sulfoxide pH=1; Stage #3: With sodium hydroxide In diethyl ether; water	94%
Stage #1: 3,5-difluorobromobenzene With potassium trimethylsilonate In diethylene glycol dimethyl ether at 120℃; for 5h; Inert atmosphere; Stage #2: With hydrogenchloride In diethylene glycol dimethyl ether; water at 20℃; Inert atmosphere;	92%
With potassium trimethylsilonate In diethylene glycol dimethyl ether at 120℃; for 5h; Inert atmosphere;	92%

3,5-difluorobromobenzene (461-96-1) → 3,5-difluoroaniline (372-39-4)

Conditions	Yield
With copper(I) oxide; 1-D-O-Methyl-chiro-inositol; ammonia; sodium hydroxide In water at 100℃; for 12h;	94%
With copper(I) oxide; ammonium hydroxide at 120℃; for 6h; Reagent/catalyst; Temperature; Autoclave; Green chemistry;	85%

3,5-difluorobromobenzene (461-96-1) + 2-bromo-3-(4-(methylthio)phenyl)-2-cyclopenten-1-one (190966-43-9) → 2-(3',5'-difluorophenyl)-3-(4'-methylthiophenyl)cyclopent-2-en-1-one (228717-97-3)

Conditions	Yield
Stage #1: With n-butyllithium In hexane at -78℃; for 0.5h; Metallation; Stage #2: With Triisopropyl borate In hexane Substitution; Suzuki coupling; Stage #3: 3,5-difluorobromobenzene; 2-bromo-3-(4-(methylthio)phenyl)-2-cyclopenten-1-one With sodium carbonate; bis-triphenylphosphine-palladium(II) chloride In water; toluene Substitution; Suzuki coupling; Heating;	93%

tetrahydrofuran (109-99-9) + 3,5-difluorobromobenzene (461-96-1) → 2-(3,5-difluorophenyl)tetrahydrofuran (1311230-64-4)

Conditions	Yield
Stage #1: tetrahydrofuran; 3,5-difluorobromobenzene With iodine; magnesium at 0 - 20℃; for 1h; Inert atmosphere; Stage #2: With iron(III) oxide In tetrahydrofuran at 0 - 20℃; for 5h; Inert atmosphere;	93%
Stage #1: 3,5-difluorobromobenzene With iodine; magnesium In tetrahydrofuran at 0 - 20℃; Inert atmosphere; Stage #2: tetrahydrofuran With iron(III) oxide at 0 - 20℃; for 5h; Inert atmosphere;	92.84%

3,5-difluorobromobenzene (461-96-1) + 9H-carbazole (86-74-8) → 9,9’-(5-bromo-1,3-phenylene)bis(9H-carbazole) (750573-24-1)

Conditions	Yield
Stage #1: 9H-carbazole With potassium tert-butylate at 120 - 140℃; Stage #2: 3,5-difluorobromobenzene for 2h;	93%
Stage #1: 9H-carbazole With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 1h; Stage #2: 3,5-difluorobromobenzene In N,N-dimethyl-formamide; mineral oil at 130℃; for 12h; Cooling with ice;	92%
With caesium carbonate In N,N-dimethyl-formamide at 170℃; for 15h;	91%

3,5-difluorobromobenzene (461-96-1) + (S)-3-methyl-piperazine-1-carboxylic acid tert-butyl ester (147081-29-6) → (S)-4-(3,5-difluoro-phenyl)-3-methyl-piperazine-1-carboxylic acid tert-butyl ester

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene at 80℃; for 3.5h; Inert atmosphere; Reflux;	93%
With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene at 110℃; for 2.5h; Inert atmosphere;

3,5-difluorobromobenzene (461-96-1) + 3,6-di(tert-butyl)-9H-carbazole (37500-95-1) → 9,9’-(5-bromo-1,3-phenylene)bis(3,6-di-tert-butyl-9H-carbazole)

Conditions	Yield
Stage #1: 3,6-di(tert-butyl)-9H-carbazole With 1,3-dimethyl-2-imidazolidinone; potassium tert-butylate at 120℃; Stage #2: 3,5-difluorobromobenzene at 150℃; for 1h; Inert atmosphere;	93%
Stage #1: 3,6-di(tert-butyl)-9H-carbazole With sodium hydride In N,N-dimethyl-formamide for 0.5h; Stage #2: 3,5-difluorobromobenzene In N,N-dimethyl-formamide for 16h; Reflux;	80.4%
With sodium hydride In N,N-dimethyl-formamide Reflux;	79.1%
With caesium carbonate In N,N-dimethyl-formamide at 60℃; for 24h;
With caesium carbonate In N,N-dimethyl-formamide at 120℃; Inert atmosphere;	59.9 g

3,5-difluorobromobenzene (461-96-1) + trimethylsilylacetylene (1066-54-2) → [2-(3,5-difluorophenyl)ethynyl]trimethylsilane (445491-09-8)

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In acetonitrile at 120℃; for 0.0833333h; Sonogashira Cross-Coupling; Microwave irradiation; Sealed tube; Inert atmosphere;	92%
With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); diethylamine In N,N-dimethyl-formamide at 120℃; for 0.25h; Inert atmosphere;	90%
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In acetonitrile at 100℃; for 16h; Inert atmosphere; Sealed tube;	80%
With copper(l) iodide; diisopropylamine; triphenylphosphine; bis-triphenylphosphine-palladium(II) chloride
With copper(l) iodide; triethylamine; tetrakis(triphenylphosphine) palladium(0) Heating;

(2RS,4SR)-4-[5-fluoro-3-(naphth-2-ylmethoxy)phenyl]-4-hydroxy-2-methyltetrahydropyran + 2-Naphthalenemethanol (1592-38-7) + 3,5-difluorobromobenzene (461-96-1) → 5-fluoro-3-(naphth-2-ylmethoxy)bromobenzene

Conditions	Yield
	92%

3,5-difluorobromobenzene (461-96-1) + phenol (108-95-2) → ((5-bromo-1,3-phenylene)bis(oxy))dibenzene (41318-73-4)

Conditions	Yield
With caesium carbonate In 1-methyl-pyrrolidin-2-one at 120℃; for 18h; Inert atmosphere;	92%
With potassium carbonate In 1-methyl-pyrrolidin-2-one at 170℃; for 10h; Inert atmosphere;	35.9 g
With potassium carbonate In 1-methyl-pyrrolidin-2-one at 170℃; for 10h; Inert atmosphere;	35.9 g
With potassium carbonate In 1-methyl-pyrrolidin-2-one at 150℃; for 48h; Inert atmosphere;	119 g
With potassium carbonate In 1-methyl-pyrrolidin-2-one at 150℃; for 48h; Inert atmosphere;	119 g

Upstream product

• 651027-03-1 (3-bromo-2,6-difluorophenyl)triethylsilane 
• 651027-05-3 (3,4-dibromo-2,6-difluorophenyl)triethylsilane 
• 651027-04-2 (3,5-dibromo-2,6-difluorophenyl)triethylsilane 
• 444-14-4 2-bromo-4,6-difluoroaniline 
• 1317-39-1 copper(I) oxide 
• 6303-21-5 hypophosphorous acid 
• 101471-20-9 2-bromo-4,6-difluoroaniline hydrobromide 
• 1435-51-4 1,3-dibromo-5-fluorobenzene 
• 367-25-9 2,4-difluorophenylamine 
• 651027-02-0 1-triethylsilyl-2,6-difluorobenzene 
• 372-18-9 1,3-Difluorobenzene 
• 184910-37-0 (4-bromo-2,6-difluorophenyl)triethylsilane 
• 372-39-4 3,5-difluoroaniline 

Downstream Products

• 455-40-3 3,5-difluorobenzoic acid 
• 330-31-4 3,5-difluoro-N-phenylbenzenamine 
• 144110-15-6 {(4R,5R)-5-[Bis-(3,5-dibromo-phenyl)-hydroxy-methyl]-2,2-dimethyl-[1,3]dioxolan-4-yl}-bis-(3,5-dibromo-phenyl)-methanol 
• 121219-23-6 1-(3,5-difluorophenyl)pentan-1-ol 
• 40161-50-0 3,5-difluoro-1-(diethoxymethylsilyl)benzene 
• 141889-59-0 ethyl 2-(N-acetyl)-5-(3,5-difluorophenyl)pent-4-ynoate 
• 64248-63-1 3,5-difluorobenzonitrile 
• 126385-68-0 ethyl 2-acetamido-4-phenylpent-4-enoate 
• 144177-92-4 {(4R,5R)-5-[Bis-(3,5-difluoro-phenyl)-hydroxy-methyl]-2,2-dimethyl-[1,3]dioxolan-4-yl}-bis-(3,5-difluoro-phenyl)-methanol 
• 130722-44-0 5-benzyloxy-3-fluorophenyl bromide 
• 445491-09-8 [2-(3,5-difluorophenyl)ethynyl]trimethylsilane 
• 84315-23-1 3,5-difluorocinnamic acid 
• 148150-92-9 1-(1-hydroxy-4-propylcyclohexyl)-3,5-difluorobenzene 
• 183065-68-1 4-bromo-2,6-difluorobenzoic acid 

Relevant articles and documents

Preparation method of 3,5-difluoroaniline

The invention discloses a preparation method of 3,5-difluoroaniline and relates to the technical field of organic synthesis. The preparation method comprises steps as follows: 2,4-difluoroaniline, tap water, hydrochloric acid, bromine, sodium nitrite, sodium monophosphate and ammonium hydroxide are taken as raw materials, cuprous oxide is taken as a catalyst, the tap water and dichloroethane are taken as solvents, and a product of 3,5-difluoroaniline is prepared through steps of bromination, diazotization, ammoniation, extraction, distillation and the like. According to the method, the industrially available raw materials can be utilized for reaction, the process is simple, post-treatment is simple and convenient, conditions are mild, environmental pollution is small, and the product of 3,5-difluoroaniline is prepared with high yield, and meanwhile, industrial production can be realized.

Convenient electrophilic fluorination of functionalized aryl and heteroaryl magnesium reagents

"Chemical Equation Presented" Cive me an "F": Electrophilic fluorination of various aromatic and heteroaromatic Grignard reagents is smoothly performed with (PhSO2)2NF as fluorinating agent in a 4:1 mixture of CH2Cl2/ perfluorodecalin (see scheme). This solvent system allows minimization of most side reactions.

Method for producing tetrakis ( fluoroaryl) borate-magnesium compound

Fluoroaryl magnesium halide is reacted with a boron compound so that a molar ratio of the fluoroaryl magnesium halide to the boron compound is not less than 3.0 and not more than 3.7, so as to produce a tetrakis (fluoroaryl) borate·magnesium compound. With this method, there occurs no hydrogen fluoride which corrodes a producing apparatus and requires troublesome waste water treatment.