540-36-3

Basic information

• Product Name: 1,4-Difluorobenzene
• Synonyms: Benzene,p-difluoro-;para-Difluorobenzene;p-difluoro-benzen;1,4-DIFLUOROBENZENE;1,4 DIFLUOROBENZENE, 1X1ML, MEOH, 2000UG /ML;1,4-DIFLUOROBENZENE, 99+%;1,4-DIFLUOROBENZENE, 1000MG, NEAT;4-Difluorobenzene
• CAS NO: 540-36-3
• Molecular Formula: C₆H₄F₂
• Molecular Weight: 114.09
• EINECS: 208-742-9
• Product Categories: Aromatic Hydrocarbons (substituted) & Derivatives;Fluorobenzene;Aryl;C6;Halogenated Hydrocarbons;Method 8020;600 Series Wastewater Methods;8000 Series Solidwaste Methods;FluoroEPA;Method 624EPA;Alpha Sort;D;DAlphabetic;DID - DINChemical Class;Fluoro;Halogenated;Volatiles/ Semivolatiles;Fluorine series;alkyl Fluorine
• Mol File: 540-36-3.mol
• Article Data: 73

Chemical Properties

• Melting Point: -13 °C
• Boiling Point: 88-89 °C(lit.)
• Flash Point: 36 °F
• Appearance: Clear colorless to slightly yellow/Liquid
• Density: 1.17
• Vapor Pressure: 63.6mmHg at 25°C
• Refractive Index: n20/D 1.441(lit.)
• Storage Temp.: Flammables area
• Solubility: 1.2g/l
• Merck: 14,3148
• BRN: 1904541
• CAS DataBase Reference: 1,4-Difluorobenzene(CAS DataBase Reference)
• NIST Chemistry Reference: 1,4-Difluorobenzene(540-36-3)
• EPA Substance Registry System: 1,4-Difluorobenzene(540-36-3)

Safety Data

• Hazard Codes: F,Xn,T
• Statements: 11-20-39/23/24/25-23/24/25
• Safety Statements: 16-29-33-7-45-36/37-7/9
• RIDADR: UN 1993 3/PG 2
• WGK Germany: 3
• RTECS: CZ5658000
• HazardClass: 3
• PackingGroup: II
• Hazardous Substances Data: 540-36-3(Hazardous Substances Data)

Usage

Chemical Properties

Clear colorless to light yellow liquid

Uses

1,4-Difluorobenzene is used in method for production of prepolymers containing Polyoxymethylene block.

InChI:InChI=1/C6H4F2/c7-5-1-2-6(8)4-3-5/h1-4H

Synthetic route

(p-fluorophenyl)trimethylsilane (455-17-4) → trimethylsilyl fluoride (420-56-4) + para-difluorobenzene (540-36-3)

Conditions	Yield
With xenon fluoride In dichloromethane Inert atmosphere;	A n/a B 100%

C6H4FN2(1+)*C6BF8(1-) (1516885-12-3) + sodium fluoride → sodium tetrafluoroborate (13755-29-8) + para-difluorobenzene (540-36-3) + C6BF14(1-)*Na(1+) + C6BF14(1-)*Na(1+)

Conditions	Yield
at 160 - 170℃; Glovebox;	A 5% B 95% C 83% D 10%

para-dinitrobenzene (100-25-4) → para-difluorobenzene (540-36-3)

Conditions	Yield
With tetrabutyl ammonium fluoride In tetrahydrofuran for 0.166667h; Inert atmosphere; Microwave irradiation;	93%

C6H4FN2(1+)*C8BF18(1-) → para-difluorobenzene (540-36-3) + C8HF15 (1516885-18-9) + C8F14 (85794-30-5) + C8BF17

Conditions	Yield
at 90 - 95℃;	A 90% B 4% C 3% D 5%

4-fluorobenzenediazonium tetrafluoroborate (459-45-0) → para-difluorobenzene (540-36-3)

Conditions	Yield
at 158 - 160℃;	86%

4-fluoroboronic acid (1765-93-1) → para-difluorobenzene (540-36-3)

Conditions	Yield
Stage #1: 4-fluoroboronic acid With sodium hydroxide In methanol at 23℃; for 0.25h; Inert atmosphere; Stage #2: With silver trifluoromethanesulfonate In methanol at 0℃; for 0.5h; Inert atmosphere; Stage #3: With Selectfluor In acetone at 23℃; for 1h; Inert atmosphere; Molecular sieve; regiospecific reaction;	85%
Multi-step reaction with 2 steps 1: diethyl ether / 20 °C / Inert atmosphere; Molecular sieve 2: silver fluoride; (tBuCN)2Cu*OTf; 1-fluoro-2,4,6-trimethylpyridinium hexafluorophosphate / tetrahydrofuran / 18 h / 50 °C / Inert atmosphere View Scheme
With potassium fluoride; copper(II) bis(trifluoromethanesulfonate) In acetonitrile at 60℃; for 20h; Sealed tube;
Multi-step reaction with 2 steps 1: potassium fluoride / acetonitrile / 16 h / 90 °C 2: 2,6-dichloro-1-fluoropyridin-1-ium tetrafluoroborate / chloroform / 6 h / 110 °C View Scheme

C6H4FN2(1+)*C6BF16(1-) (1516885-15-6) → perfluorohexyldifluoroborane (329009-01-0) + para-difluorobenzene (540-36-3)

Conditions	Yield
at 110 - 115℃;	A 85% B 67%

C6H4FN2(1+)*C12BF28(1-) (1516885-16-7) → para-difluorobenzene (540-36-3) + C12BF27 (1516885-19-0)

Conditions	Yield
at 140 - 145℃;	A 79% B 85%

1,4-phenylenediamine (106-50-3) → para-difluorobenzene (540-36-3)

Conditions	Yield
With hydrogenchloride; tetrafluoroboric acid; sodium nitrite In water at 50℃; for 0.0166667h; Temperature; Large scale;	83%
With pyridine hydrogenfluoride; sodium nitrite 1.) O deg C, 20 min, 2.) 120 deg C, 1 h;	65%
With pyridine; hydrogen fluoride; sodium nitrite 1.) room temperature, 2.) 0 deg C, 3.) 120 deg C; Yield given. Multistep reaction;

C6H4FN2(1+)*C12BF28(1-) (1516885-16-7) + sodium fluoride → sodium tetrafluoroborate (13755-29-8) + para-difluorobenzene (540-36-3) + C12BF28(1-)*Na(1+) (1516885-26-9) + C12BF28(1-)*Na(1+) (1516885-25-8)

Conditions	Yield
at 25 - 200℃; for 0.133333h; Glovebox;	A 17% B 81% C 39% D 33%

C6H4FN2(1+)*C6BF14(1-) → para-difluorobenzene (540-36-3) + perfluoro-trans-hex-1-enyldifluoroborane (375856-42-1)

Conditions	Yield
at 80 - 90℃;	A 80% B 49%

C6H4FN2(1+)*C6BF8(1-) (1516885-12-3) + sodium fluoride → sodium tetrafluoroborate (13755-29-8) + para-difluorobenzene (540-36-3) + C6BF8(1-)*Na(1+) (1516885-20-3)

Conditions	Yield
at 160 - 170℃; Glovebox;	A 11% B 79% C 71%

4-Fluorophenol (371-41-5) → para-difluorobenzene (540-36-3)

Conditions	Yield
With 1,3-bis(2,6-diisopropylphenyl)-2,2-difluoro-2,3-dihydro-1h-imidazole; cesium fluoride; diphenylzinc In toluene at 110℃; for 20h; Product distribution / selectivity; Sealed vial;	78%
With 1,3-bis(2,6-diisopropylphenyl)-2,2-difluoro-2,3-dihydro-1h-imidazole; cesium fluoride In toluene at 23 - 110℃; for 20.5h; Inert atmosphere;	74 %Spectr.

C6H4FN2(1+)*C8BF18(1-) + sodium fluoride → sodium tetrafluoroborate (13755-29-8) + para-difluorobenzene (540-36-3) + C8F14 (85794-30-5) + C8BF18(1-)*Na(1+) + C8BF18(1-)*Na(1+)

Conditions	Yield
at 160 - 170℃; Glovebox;	A 17% B 77% C 3% D 65% E 12%

C6H4FN2(1+)*C3BF6(1-) (1516885-17-8) + sodium fluoride → sodium tetrafluoroborate (13755-29-8) + para-difluorobenzene (540-36-3) + C3BF6(1-)*Na(1+) (1516885-27-0) + C3HF3*Na(1+)

Conditions	Yield
at 160 - 170℃; Glovebox;	A 76% B 51% C 9% D 76%

(p-fluorophenyl)trimethylsilane (455-17-4) → para-difluorobenzene (540-36-3)

Conditions	Yield
With xenon difluoride In dichloromethane at 20℃; for 1h; Pyrex vessel;	73%
With lead(IV) acetate; boron trifluoride diethyl etherate Ambient temperature;	43 % Chromat.

potassim 4-fluorophenyltrifluoroborate → fluorobenzene (462-06-6) + para-difluorobenzene (540-36-3)

Conditions	Yield
With lithium hydroxide monohydrate; silver trifluoromethanesulfonate; Selectfluor In ethyl acetate at 55℃; Sealed tube;	A n/a B 65%

4-fluoroaniline (371-40-4) → para-difluorobenzene (540-36-3)

Conditions	Yield
With sodium nitrite In Et3N-3HF	63.1%
With HF; sodium nitrite In tetrahydrofuran; ice-salt water	40%

Pentafluorobenzene (363-72-4) → para-difluorobenzene (540-36-3) + 1,2,4,5-Tetrafluorobenzene (327-54-8) + 1,2,4-trifluorobenzene (367-23-7)

Conditions	Yield
With C32H46N2Ru; sodium carbonate; isopropyl alcohol at 70℃; for 4h; Inert atmosphere; Schlenk technique; Glovebox;	A 7% B 60% C 21%

C6H4FN2(1+)*C6BF8(1-) (1516885-12-3) → para-difluorobenzene (540-36-3) + Pentafluorobenzene (363-72-4) + decafluorobiphenyl (434-90-2)

Conditions	Yield
at 95 - 100℃;	A 54% B 24% C 16%

p-fluorophenyl-lead(IV) triacetate + trifluoroborane diethyl ether (109-63-7) → fluorobenzene (462-06-6) + CH3COO(1-)*BF2(1+)=CH3COOBF2 + para-difluorobenzene (540-36-3) + lead acetate (301-04-2)

Conditions	Yield
Stirring of Pb-compd. in excess of BF3*Et2O overnight at room temp.; GC anal.;	A 7% B n/a C 49% D n/a

4-fluorophenyl trifluoromethanesulfonate (132993-23-8) → para-difluorobenzene (540-36-3)

Conditions	Yield
With 18-crown-6 ether; tetramethlyammonium chloride; cesium fluoride In acetonitrile at 60℃; for 16h; Glovebox;	49%

benzene (71-43-2) → fluorobenzene (462-06-6) + para-difluorobenzene (540-36-3) + ortho-difluorobenzene (367-11-3) + 3,3,6-trifluoro-1,4-cyclohexadiene (74298-20-7) + cis-3,6-difluorocyclohexadiene (74298-19-4) + trans,cis,trans-3,4,5,6-tetrafluorocyclohexene (74298-17-2)

Conditions	Yield
With silver(II) fluoride In hexane at 40℃; for 0.2h; Product distribution; Mechanism; other solvents, times, temperatures, ratios;	A 47% B 2.3% C 1.9% D 6.3% E 4.1% F 7.4%

1,2,4,5-Tetrafluorobenzene (327-54-8) → para-difluorobenzene (540-36-3) + 1,2,4-trifluorobenzene (367-23-7)

Conditions	Yield
Stage #1: 1,2,4,5-Tetrafluorobenzene With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; [(HC[(CMe)N(2,4,6-Me3C6H2)]2)Al(H)2] In benzene-d6; benzene at 100℃; for 8h; Inert atmosphere; Glovebox; Sealed tube; Stage #2: With methanol In benzene-d6; benzene at 100℃; for 2h; Catalytic behavior; Inert atmosphere; Glovebox; Sealed tube; regioselective reaction;	A 19.5% B 47%

(p-fluorophenyl)trimethylsilane (455-17-4) + lead(IV) tetraacetate (546-67-8) + trifluoroborane diethyl ether (109-63-7) → fluorobenzene (462-06-6) + para-difluorobenzene (540-36-3)

Conditions	Yield
Stirring of silane with a slurry of Pb(OAc)4 in excess of BF3*Et2O overnight at room temp.; GC anal.;	A 0% B 43%

1-Chloro-4-fluorobenzene (352-33-0) → para-difluorobenzene (540-36-3) + ortho-difluorobenzene (367-11-3)

Conditions	Yield
With Al2CuF8 at 500℃; Gas phase; Inert atmosphere;	A 42% B 11%

1-Chloro-4-fluorobenzene (352-33-0) → 1,3-Difluorobenzene (372-18-9) + para-difluorobenzene (540-36-3)

Conditions	Yield
With Al2CuF8 at 500℃; Inert atmosphere;	A 11% B 42%

1-chloro-2-fluorobenzene (348-51-6) → fluorobenzene (462-06-6) + 1,3-Difluorobenzene (372-18-9) + para-difluorobenzene (540-36-3) + ortho-difluorobenzene (367-11-3)

Conditions	Yield
With Al2CuF8 at 500℃; Gas phase; Inert atmosphere;	A 39% B 21% C 7% D 16%
With Al2CuF8 at 500℃; Inert atmosphere;	A 39% B 21% C 7% D 16%

1,2,3,5-tetrafluorobenzene (2367-82-0) → 1,2,3-trifluorobenzene (1489-53-8) + 1,3-Difluorobenzene (372-18-9) + para-difluorobenzene (540-36-3) + ortho-difluorobenzene (367-11-3) + 1,2,4-trifluorobenzene (367-23-7)

Conditions	Yield
Stage #1: 1,2,3,5-tetrafluorobenzene With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; [(HC[(CMe)N(2,4,6-Me3C6H2)]2)Al(H)2] In benzene-d6; benzene at 100℃; for 8h; Inert atmosphere; Glovebox; Sealed tube; Stage #2: With methanol In benzene-d6; benzene at 100℃; for 2h; Catalytic behavior; Inert atmosphere; Glovebox; Sealed tube; Overall yield = 69.5 %; regioselective reaction;	A 8.5% B 9.5% C 7% D 5.5% E 39%

para-difluorobenzene (540-36-3) + 5-methyl-dihydro-furan-2-one (108-29-2) → 5,8-difluoro-4-methyl-3,4-dihydronaphthalen-1(2H)-one (77263-70-8)

Conditions	Yield
Stage #1: para-difluorobenzene; 5-methyl-dihydro-furan-2-one With aluminum (III) chloride Heating / reflux; Stage #2: With hydrogenchloride In water at 0℃;	100%
With aluminum (III) chloride for 16h; Heating / reflux;	81%
With aluminium trichloride for 16h; Heating;	55%

para-difluorobenzene (540-36-3) + 1,1,4,4-tetrakis(trimethylsilyl)butane-1,4-diylsilylene (250665-62-4) → 7,10-difluoro-1,1,4,4-tetrakis-trimethylsilanyl-5-sila-spiro[4.6]undeca-6,8,10-triene

Conditions	Yield
Irradiation;	100%

para-difluorobenzene (540-36-3) → 1,4-difluoro-2-nitrobenzene (364-74-9)

Conditions	Yield
With sulfuric acid; nitric acid at 30 - 70℃; for 0.0333333h; Large scale;	98%
With 2C2H3F3O*BF3; potassium nitrate at 20℃; for 6h;	84%
With sulfuric acid; potassium nitrate at 5℃; Large scale;	83%

2-bromonaphthalene (580-13-2) + para-difluorobenzene (540-36-3) → C16H10F2

Conditions	Yield
With rubidium carbonate; 2,2-dimetyl-3-(adamantan-1-yl)propanoic acid; palladium dichloride In N,N-dimethyl acetamide at 60℃; for 40h; Inert atmosphere; Schlenk technique;	98%

para-difluorobenzene (540-36-3) + para-methylphenylmagnesium bromide (4294-57-9) → 1,4-bis(p-tolyl)benzene (97295-31-3)

Conditions	Yield
With C35H31BrN4NiP In tetrahydrofuran at 25℃; for 13h; Schlenk technique; Inert atmosphere;	97%
With C26H24ClN2NiP*0.1C7H8 In toluene at 25℃; for 24h; Kumada Cross-Coupling; Schlenk technique; Inert atmosphere;	74%

para-difluorobenzene (540-36-3) + 4-methoxyphenyl magnesium bromide (13139-86-1) → 4,4-dimethoxy-1,1':4',1-terphenyl (13021-19-7)

Conditions	Yield
With C35H31BrN4NiP In tetrahydrofuran at 25℃; for 12h; Schlenk technique; Inert atmosphere;	97%

para-difluorobenzene (540-36-3) + 4-dimethylaminophenylmagnesium bromide (7353-91-5) → 4-[4-(4-dimethylaminophenyl)phenyl]-N,N-dimethylaniline (34614-43-2)

Conditions	Yield
With C35H31BrN4NiP In tetrahydrofuran at 25℃; for 12h; Schlenk technique; Inert atmosphere;	97%

ortho-tolylmagnesium bromide (932-31-0) + para-difluorobenzene (540-36-3) → 2,2”-dimethyl-1,1‘:4’,1“-terphenyl (53092-64-1)

Conditions	Yield
With C35H31BrN4NiP In tetrahydrofuran at 70℃; for 22h; Schlenk technique; Inert atmosphere;	97%

carbon disulfide (75-15-0) + para-difluorobenzene (540-36-3) + benzyl bromide (100-39-0) → benzyl 2,5-difluorobenzodithioate

Conditions	Yield
Stage #1: para-difluorobenzene With sec.-butyllithium; copper(l) cyanide In hexane; cyclohexane at -78℃; for 3h; Schlenk technique; Inert atmosphere; Stage #2: carbon disulfide In hexane; cyclohexane at -50 - 20℃; for 1h; Schlenk technique; Inert atmosphere; Stage #3: benzyl bromide In hexane; cyclohexane at 20℃; for 4h; Schlenk technique; Inert atmosphere;	97%

para-difluorobenzene (540-36-3) + 4-<(2S)-2-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)propionyl>morpholine (135206-86-9) → (2S)-1-(2,5-difluoro-phenyl)-2-(tetrahydro-pyran-2-yloxy)-propan-1-one (939439-00-6)

Conditions	Yield
Stage #1: para-difluorobenzene; 4-<(2S)-2-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)propionyl>morpholine With lithium diisopropyl amide In tetrahydrofuran; n-heptane at 0℃; for 2.333h; Stage #2: With ammonium chloride In tetrahydrofuran; n-heptane; water	96.2%

para-difluorobenzene (540-36-3) → 2-bromo-1,4-difluorobenzene (399-94-0)

Conditions	Yield
With N-Bromosuccinimide; boron trifluoride at 20℃; for 6h;	96%
With N-Bromosuccinimide; sulfuric acid at 30 - 40℃; for 1h; Large scale;	92.7%

tert-butylethylene (558-37-2) + para-difluorobenzene (540-36-3) → C12H16F2

Conditions	Yield
With sodium acetylacetonate; C107H126N2NiO2; sodium hydride In neat (no solvent) at 120℃; for 24h; Reagent/catalyst; regioselective reaction;	96%

2-bromobenzoic acid methyl ester (610-94-6) + para-difluorobenzene (540-36-3) → C14H10F2O2

Conditions	Yield
With rubidium carbonate; 2,2-dimetyl-3-(adamantan-1-yl)propanoic acid; palladium dichloride In N,N-dimethyl acetamide at 60℃; for 40h; Inert atmosphere; Schlenk technique;	96%

para-difluorobenzene (540-36-3) + [2,6-diisopropylbenzene-β-diketiminate]Nb(NtBu)(η6-C6H6) → C39H54F2N3Nb

Conditions	Yield
With trimethoxybenzene In benzene-d6 at 60℃; for 2h;	95%

3-phthalimido-1-propene (5428-09-1) + para-difluorobenzene (540-36-3) → C17H11F2NO2

Conditions	Yield
With silver(I) acetate; palladium diacetate In dimethyl sulfoxide at 130℃; for 4h; Sealed tube; regioselective reaction;	95%

para-difluorobenzene (540-36-3) + 1-Bromonaphthalene (90-11-9) → 1-(2,5-difluorophenyl)naphthalene

Conditions	Yield
With rubidium carbonate; 2,2-dimetyl-3-(adamantan-1-yl)propanoic acid; palladium dichloride In N,N-dimethyl acetamide at 60℃; for 40h; Inert atmosphere; Schlenk technique;	95%

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%

para-difluorobenzene (540-36-3) + benzaldehyde (100-52-7) → 4-fluorobenzhydrol (149099-27-4, 149243-88-9, 365-22-0)

Conditions	Yield
With calcium In tetrahydrofuran at -78℃; for 0.5h;	93%

2-(hydroxymethyl)-1H-isoindole-1,3(2H)-dione (118-29-6) + para-difluorobenzene (540-36-3) → 2-(2,5-difluorobenzyl)isoindoline-1,3-dione

Conditions	Yield
With trifluorormethanesulfonic acid Ambient temperature;	92%

para-difluorobenzene (540-36-3) + benzaldehyde (100-52-7) → (2,5-difluorophenyl)(phenyl)methanol

Conditions	Yield
Stage #1: para-difluorobenzene With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran; hexane at -71 - -68℃; for 1.5h; Stage #2: benzaldehyde In tetrahydrofuran; hexane at -71 - -68℃; for 1h;	92%

para-difluorobenzene (540-36-3) + phenylmagnesium bromide → [1,1';4',1'']terphenyl (92-94-4)

Conditions	Yield
With 1-[2-(diphenylphosphino)phenyl]ethanol; bis(acetylacetonate)nickel(II) In diethyl ether at 20℃; for 1h;	92%

para-difluorobenzene (540-36-3) + phenylmagnesium bromide (100-58-3) → [1,1';4',1'']terphenyl (92-94-4)

Conditions	Yield
Stage #1: para-difluorobenzene; phenylmagnesium bromide; 1-[2-(diphenylphosphino)phenyl]ethanol; bis(acetylacetonate)nickel(II) In diethyl ether for 1h; Stage #2: With methanol In diethyl ether Product distribution / selectivity;	92%
With nickel(II) chloride hexahydrate; C32H39N2OP In tetrahydrofuran at 25℃; for 20h; Kumada coupling reaction; Inert atmosphere;	92%
Stage #1: para-difluorobenzene; phenylmagnesium bromide; bis(acetylacetonate)nickel(II); ((2-hydroxymethyl)phenyl)diphenylphosphine In diethyl ether for 2h; Stage #2: With methanol In diethyl ether Product distribution / selectivity;	92 %Chromat.

para-difluorobenzene (540-36-3) + N-Methyl-N-methoxy-4-chlorobutanamide (64214-66-0) → 4‐chloro‐1‐(2,5-difluorophenyl)butan-1-one (1216260-42-2)

Conditions	Yield
Stage #1: para-difluorobenzene With n-butyllithium In tetrahydrofuran at -70 - -60℃; for 3h; Stage #2: N-Methyl-N-methoxy-4-chlorobutanamide In tetrahydrofuran at -70 - 20℃; for 2h;	91.33%

[(tris(3,5-dimethylpyrazolyl)borate)RhH2(PPhMe2)] + para-difluorobenzene (540-36-3) → [(tris(3,5-dimethylpyrazolyl)borate)RhH(κ2-C6H4-2-PMe2)] (1258937-61-9) + [Rh(tris(3,5-dimethylpyrazolyl)borate)H(2,5-C6F2H3)(PMe2Ph)] (1258937-80-2)

Conditions	Yield
In neat (no solvent) Irradiation (UV/VIS); (N2, Schlenk) a soln. of complex in fluorobenzene-compound in NMR tube was irradiated for 5 h, heated at 120°C for 1 h; flash chromy. (silica gel, 5:1 hexane-THF), washed with a min amount of ice-cold hexane; elem. anal.;	A n/a B 91%

3-pyridinecarboxaldehyde (500-22-1) + para-difluorobenzene (540-36-3) → (2,5-difluorophenyl)(pyridin-3-yl)methanol

Conditions	Yield
Stage #1: para-difluorobenzene With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran at -70℃; Stage #2: 3-pyridinecarboxaldehyde In tetrahydrofuran at -70℃; for 1h;	90%

cyclohexanedione monoethylene ketal (4746-97-8) + para-difluorobenzene (540-36-3) → 8-(2,5-difluorophenyl)-1,4-dioxaspiro[4.5]decan-8-ol

Conditions	Yield
Stage #1: para-difluorobenzene With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran at -70℃; Stage #2: cyclohexanedione monoethylene ketal In tetrahydrofuran at -70℃; for 1h;	90%

Upstream product

• 462-06-6 fluorobenzene 
• 106-46-7 para-dichlorobenzene 
• 108-90-7 chlorobenzene 
• 106-50-3 1,4-phenylenediamine 
• 373-91-1 hypofluorous acid trifluoromethyl ester 
• 71-43-2 benzene 
• 372-18-9 1,3-Difluorobenzene 
• 367-11-3 ortho-difluorobenzene 
• 367-23-7 1,2,4-trifluorobenzene 
• 455-17-4 (p-fluorophenyl)trimethylsilane 
• 460-00-4 1-Bromo-4-fluorobenzene 
• 352-33-0 1-Chloro-4-fluorobenzene 
• 348-51-6 1-chloro-2-fluorobenzene 
• 67-56-1 methanol 

Downstream Products

• 5905-01-1 5,5'-diformyl-2,2'-difuran 
• 99113-87-8 2-formyl-4-(2,5-difluorophenyl)furan 
• 99113-90-3 2-formyl-5-(2,5-difluorophenyl)furan 
• 144782-93-4 methyl 4-<2-(2,5-difluorobenzyl)benzoyl>-2,5-dimethylpyrrole-3-carboxylate 
• 144511-13-7 6,9-difluorobenzoisoquinoline-5,10-dione 
• 144511-12-6 3-(2',5'-difluorobenzoyl)isonicotinic acid 
• 144511-11-5 4-(2',5'-Difluorobenzoyl)nicotinic acid 
• 154029-44-4 6,9-difluorobenzoquinoline-5,10-dione 
• 145047-51-4 2-(2,5-difluorobenzoyl)nicotinic acid 
• 126707-05-9 4-(2,5-Difluoro-benzoyl)-thiophene-3-carboxylic acid 
• 145047-52-5 2-(2'5'-difluorobenzoyl)pyrazine-3-carboxylic acid 
• 84564-77-2 1,4-Difluoro-2-isopropyl-benzene 
• 2991-28-8 2,5-difluorobenzoic acid 
• 149099-27-4 4-fluorobenzhydrol 

Relevant articles and documents

Metal-Free Photoredox-Catalyzed Hydrodefluorination of Fluoroarenes Utilizing Amide Solvent as Reductant

A metal-free photoredox-catalyzed hydrodefluorination of fluoroarenes was achieved by using N,N,N’,N’-tetramethyl-para-phenylenediamine (1) as a strong photoreduction catalyst. This reaction was applicable not only to electron-rich monofluoroarenes but also to polyfluoroarenes to afford non-fluorinated arenes. The experimental mechanistic studies indicated that the amide solvent NMP plays an important role for regeneration of the photocatalyst, enabling additive-free photoreduction catalysis.

Nucleophilic Fluorination of Heteroaryl Chlorides and Aryl Triflates Enabled by Cooperative Catalysis

Aryl and heteroaryl fluorides are growing to be dominant motifs in pharmaceuticals and agrochemicals, yet they are rare in both nature and commodity chemicals. As a consequence, there is an increasingly urgent need to develop mild, cost-effective, and scalable methods for fluorination. The most straightforward route to synthesize aryl fluorides is through the halide exchange "halex"reaction, but conditions, cost, and atom economy preclude most available methods from large-scale manufacturing processes. We report a new approach that leverages the cooperative action of 18-crown-6 ether and tetramethylammonium chloride to catalytically access the reactivity of tetramethylammonium fluoride and achieve halex fluorinations under mild conditions with operational ease. The described methodology readily converts both heteroaryl chlorides and aryl triflates to their corresponding (hetero)aryl fluorides in high yields and purities.

Novel manufacturing method of fluoro-aryl compounds and derivatives thereof

The invention relates to a novel method of manufacturing fluoro-aryl compounds and derivatives thereof, in particular, fluorobenzene and derivatives thereof. The production environment of the manufacturing method is environmentally friendly. The shortages of a conventional method are overcome through a simple and beneficial mode. Compared with the prior art, the provided method is more effective,more environmentally friendly, and more energy saving. The method is used to produce core fluorinated aromatic compounds, preferably, core fluorinated fluorobenzene. On one aspect, the invention provides a method, which is advantages in industry and uses HF and a halogenated benzene precursor to prepare fluorobenzene and hydrogen halide. Moreover, the invention provides chlorobenzene as the primary raw material to prepare fluorobenzene, which is an important material in industry, and a beneficial, unexpected and simple application of chlorobenzene. In the prior art, the provided application ofchlorobenzene is unknown.