95-52-3

Basic information

• Product Name: 2-Fluorotoluene
• Synonyms: 1-Fluor-2-methylbenzol;1-fluoro-2-methyl-benzen;1-Fluoro-2-methylbenzene;1-fluoro-2-methyl-benzene;1-Methyl-2-fluorobenzene;2-fluoromethylbenzene;Benzene,1-fluoro-2-methyl-;benzene,2-fluoro-1-methyl-
• CAS NO: 95-52-3
• Molecular Formula: C7H7F
• Molecular Weight: 110.13
• EINECS: 202-428-5
• Product Categories: Aromatic Hydrocarbons (substituted) & Derivatives;Organics;Aryl;C7;Halogenated Hydrocarbons;organofluorine compounds;Aryl Fluorinated Building Blocks;Building Blocks;C7-C8;Chemical Synthesis;Fluorinated Building Blocks;Halogenated Hydrocarbons;Organic Building Blocks;Organic Fluorinated Building Blocks;Other Fluorinated Organic Building Blocks;alkyl Fluorine
• Mol File: 95-52-3.mol
• Article Data: 69

Chemical Properties

• Melting Point: -62 °C
• Boiling Point: 113-114 °C(lit.)
• Flash Point: 55 °F
• Appearance: Clear colorless to slightly yellow/Liquid
• Density: 1.001 g/mL at 25 °C(lit.)
• Vapor Density: 3.8 (vs air)
• Vapor Pressure: 21 mm Hg ( 20 °C)
• Refractive Index: n20/D 1.473(lit.)
• Storage Temp.: Flammables area
• Explosive Limit: 1.3%(V)
• Water Solubility: immiscible
• Merck: 14,4180
• BRN: 1853362
• CAS DataBase Reference: 2-Fluorotoluene(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Fluorotoluene(95-52-3)
• EPA Substance Registry System: 2-Fluorotoluene(95-52-3)

Safety Data

• Hazard Codes: F,Xi
• Statements: 11-36/37/38
• Safety Statements: 16-26-33-36-37/39
• RIDADR: UN 2388 3/PG 2
• WGK Germany: 3
• RTECS: XT2579000
• TSCA: Yes
• HazardClass: 3
• PackingGroup: II
• Hazardous Substances Data: 95-52-3(Hazardous Substances Data)

Usage

Chemical Properties

clear colorless to slightly yellow liquid

Uses

It is employed in organic synthesis.

General Description

A colorless liquid with an aromatic odor. May sink or float on water.

Air & Water Reactions

Highly flammable. Insoluble in water.

Reactivity Profile

2-Fluorotoluene is of generally low reactivity. Reacts with strong oxidizing agents and strong reducing agents. Also may be incompatible with many amines, nitrides, azo/diazo compounds, alkali metals, and epoxides [USCG, 1999].

Health Hazard

Inhalation of vapor may cause respiratory irritation. Prolonged and repeated vapor exposures may produce systemic toxic effects.

Purification Methods

Dry o-fluorotoluene with P2O5 or CaSO4 and fractionally distil it through a silvered vacuum-jacketed glass column with 1/8th-in glass helices. A high reflux ratio is necessary because of the closeness of the boiling points of the o-, m-and p-isomers [Potter & Saylor J Am Chem Soc 37 90 1951]. [Beilstein 5 H 290, 5 III 676, 5 IV 799.]

Synthetic route

o-toluidine (95-53-4) → 2-Fluorotoluene (95-52-3)

Conditions	Yield
With pyridine hydrogenfluoride; sodium nitrite 1.) O deg C, 20 min, 2.) 55 deg C, 1 h;	99%
With hydrogen fluoride; sodium nitrite at -1 - 3℃; for 1h;	99.5%
Stage #1: o-toluidine With hydrogen fluoride at -15 - 0.5℃; Flow reactor; Large scale; Stage #2: With nitrosylsulfuric acid at -5 - 0.5℃; Flow reactor; Large scale;	98.1%

ortho-methylphenyl iodide (615-37-2) → 2-Fluorotoluene (95-52-3)

Conditions	Yield
With copper(I) trifluoromethanesulfonate bis(trimethylacetonitrile) complex; silver fluoride In N,N-dimethyl-formamide at 140℃; for 22h; Inert atmosphere;	96%

o-fluorobenzyl bromide (446-48-0) → 2-Fluorotoluene (95-52-3) + 9,10-dihydrophenanthrene (776-35-2) + 1,2-bis(2-fluorophenyl)ethane (349-38-2)

Conditions	Yield
With magnesium at 600℃;	A 11% B 3% C 80%

trifluorormethanesulfonic acid (1493-13-6) + 2-methylphenyl diazonium tetrafluoroborate (2093-46-1) → 2-Fluorotoluene (95-52-3) + 2-methylphenyl triflate (66107-34-4)

Conditions	Yield
at 90℃; for 1h;	A n/a B 75%

2-fluorobenzyl chloride (345-35-7) → 2-Fluorotoluene (95-52-3) + 9,10-dihydrophenanthrene (776-35-2) + 1,2-bis(2-fluorophenyl)ethane (349-38-2)

Conditions	Yield
With magnesium at 600℃;	A 7% B 5% C 73%

toluene-2-diazonium ; hexafluoro phosphate (19296-22-1) → 2-Fluorotoluene (95-52-3)

Conditions	Yield
With boron trifluoride diethyl etherate at 120 - 125℃; for 1h;	72%

ortho-cresol (95-48-7) → 2-Fluorotoluene (95-52-3)

Conditions	Yield
With 1,3-bis(2,6-diisopropylphenyl)-2,2-difluoro-2,3-dihydro-1h-imidazole; cesium fluoride; diphenylzinc In 1,4-dioxane at 110℃; for 20h; Product distribution / selectivity; Sealed vial;	72%
With 1,3-bis(2,6-diisopropylphenyl)-2,2-difluoro-2,3-dihydro-1h-imidazole; diphenylzinc; cesium fluoride In 1,4-dioxane at 23 - 110℃; for 20.5h; Inert atmosphere;	87 %Spectr.

para-chlorotoluene (106-43-4) → p-fluorotoluene (352-32-9) + 2-Fluorotoluene (95-52-3) + m-Fluorotoluene (352-70-5)

Conditions	Yield
With Al2CuF8 Gas phase; Inert atmosphere;	A 71% B 5% C 10%
With silver fluoride at 350℃; Product distribution / selectivity; Gas phase;	A 20.8% B 0.6% C 35.8%

potassium o-tolyltrifluoroborate → 2-Fluorotoluene (95-52-3) + toluene (108-88-3)

Conditions	Yield
With lithium hydroxide monohydrate; silver trifluoromethanesulfonate; Selectfluor In ethyl acetate at 55℃; Sealed tube;	A 71% B n/a

2-methylchlorobenzene (95-49-8) → 2-Fluorotoluene (95-52-3) + m-Fluorotoluene (352-70-5)

Conditions	Yield
With Al2CuF8 Gas phase; Inert atmosphere;	A 60% B 7%

(2-tolyl)tributyltin (68971-87-9) → 2-Fluorotoluene (95-52-3)

Conditions	Yield
With copper(II) bis(trifluoromethanesulfonate); tetrabutylammonium triphenyldifluorosilicate In acetonitrile at 60℃; for 3h; Sealed tube; regiospecific reaction;	50%
With copper(I) trifluoromethanesulfonate bis(trimethylacetonitrile) complex; 1-fluoro-2,4,6-trimethylpyridinium trifluoromethanesulfonate In ethyl acetate at 25℃; for 12h; Inert atmosphere; Glovebox;	76 %Spectr.

lead(IV) tetraacetate (546-67-8) + trifluoroborane diethyl ether (109-63-7) + toluene (108-88-3) → p-fluorotoluene (352-32-9) + 2-Fluorotoluene (95-52-3) + m-Fluorotoluene (352-70-5)

Conditions	Yield
mercury(II) diacetate Stirring of toluene in BF3*Et2O contg. Pb(OAc)4 and overnight at room temp.; GC anal. 13% recovery of toluene.;	A 43% B 12% C 4%

2-methylphenyl triflate (66107-34-4) → 2-Fluorotoluene (95-52-3)

Conditions	Yield
With bis[(trimethylsilyl)methyl](1,5-cyclooctadiene)palladium(II); t-BuBrettPhos; cesium fluoride In toluene at 130℃; for 12h;	42%
With bis[(trimethylsilyl)methyl](1,5-cyclooctadiene)palladium(II); t-BuBrettPhos; cesium fluoride In toluene at 130℃; for 12h;	42 %Chromat.

2-Fluorobenzaldehyde (446-52-6) → benzimidazole (271-44-3) + 2-Fluorotoluene (95-52-3)

Conditions	Yield
With hydrazine hydrate In 1,2-dimethoxyethane for 15h; Heating;	A 29% B 45 % Chromat.

1-chloro-3-methylbenzene (108-41-8) → p-fluorotoluene (352-32-9) + 2-Fluorotoluene (95-52-3) + m-Fluorotoluene (352-70-5)

Conditions	Yield
With silver fluoride at 350℃; Product distribution / selectivity; Gas phase;	A 15% B 6.7% C 25.7%

2-methylchlorobenzene (95-49-8) → p-fluorotoluene (352-32-9) + 2-Fluorotoluene (95-52-3) + m-Fluorotoluene (352-70-5)

Conditions	Yield
With silver fluoride at 350℃; Product distribution / selectivity; Gas phase;	A 0.5% B 13.9% C 14.4%

fluorobenzene (462-06-6) + Methyl fluoride (593-53-3) → p-fluorotoluene (352-32-9) + 2-Fluorotoluene (95-52-3) + m-Fluorotoluene (352-70-5)

Conditions	Yield
at 37.5℃; Product distribution; Irradiation; various fluorobenzenes, other conditions;

Chlorodifluoromethane (75-45-6) → fluorobenzene (462-06-6) + p-fluorotoluene (352-32-9) + 2-Fluorotoluene (95-52-3) + m-Fluorotoluene (352-70-5) + benzene (71-43-2)

Conditions	Yield
With methylcyclopentadiene at 650.9℃; Product distribution; Mechanism; conditions of pulse gas compression, other temperatures;

Methyl formate (107-31-3) + C7H7F*H(1+) (138850-94-9) → 2-Fluorotoluene (95-52-3) + C2H4O2*H(1+) (39014-35-2, 380649-05-8, 52067-01-3)

Conditions	Yield
Thermodynamic data;

benzyltrimethylsilane (770-09-2) → 2-Fluorotoluene (95-52-3)

Conditions	Yield
With fluorine In trichlorofluoromethane at -78℃;

C7H7F*H(1+) (138850-94-9) + toluene (108-88-3) → 2-Fluorotoluene (95-52-3) + C7H8*H(1+) (52809-63-9)

Conditions	Yield
Thermodynamic data;

1-Fluoro-2-methyl-benzene; compound with GENERIC INORGANIC NEUTRAL COMPONENT + toluene (108-88-3) → 2-Fluorotoluene (95-52-3) + Toluene; compound with GENERIC INORGANIC NEUTRAL COMPONENT (77406-15-6)

Conditions	Yield
Thermodynamic data;

toluene (108-88-3) → p-fluorotoluene (352-32-9) + 2-Fluorotoluene (95-52-3)

Conditions	Yield
With Selectfluor In acetonitrile for 16h; Heating; also fluorination of other aromatic compounds;	A 20 % Spectr. B 60 % Spectr.
With potassium hydroxide; nitrogen; fluorine In methanol at -40℃; Product distribution; different educt and reagent concentration, different temperatures, different fluorine/nitrogen ratio, different solvents, without or with different additives;	A 57.0 % Chromat. B 32.7 % Chromat.
With acetyl hypofluorite for 2h;
With trifluorormethanesulfonic acid; Selectfluor In dichloromethane at 40℃; for 24h; Fluorination; Title compound not separated from byproducts;

toluene (108-88-3) → p-fluorotoluene (352-32-9) + 2-Fluorotoluene (95-52-3) + m-Fluorotoluene (352-70-5)

Conditions	Yield
With fluorine In trichlorofluoromethane at -78℃; for 1h; Rate constant; Product distribution; competitive reaction with benzene, other solvent;	A 29 % Chromat. B 60 % Chromat. C 11 % Chromat.
With lead(IV) acetate; boron trifluoride diethyl etherate; mercury(II) diacetate Ambient temperature;	A 43 % Chromat. B 12 % Chromat. C 4 % Chromat.
With caesium fluoroxysulphate; trifluorormethanesulfonic acid In acetonitrile Ambient temperature; Yield given;

toluene (108-88-3) → p-fluorotoluene (352-32-9) + 2-Fluorotoluene (95-52-3) + m-Fluorotoluene (352-70-5) + benzyl fluoride (350-50-5)

Conditions	Yield
With acetyl hypofluorite In acetic acid for 0.0833333h; Ambient temperature; Yield given. Yields of byproduct given;
With fluorine In acetonitrile at 0℃; Flow reactor;

toluene (108-88-3) → p-fluorotoluene (352-32-9) + 2-Fluorotoluene (95-52-3) + m-Fluorotoluene (352-70-5) + 2,4-difluorotoluene (452-76-6)

Conditions	Yield
With tetrafluoroammonium tetrafluoroborate In hydrogen fluoride at 0℃; Further byproducts given. Title compound not separated from byproducts;	A 15 % Spectr. B 15 % Spectr. C 8 % Spectr. D 30 % Spectr.

toluene (108-88-3) → p-fluorotoluene (352-32-9) + 2-Fluorotoluene (95-52-3) + m-Fluorotoluene (352-70-5) + 2,4-difluorotoluene (452-76-6) + 2,3,4,6-tetrafluorotoluene

Conditions	Yield
With tetrafluoroammonium tetrafluoroborate In hydrogen fluoride at 0℃; Product distribution;	A 15 % Spectr. B 15 % Spectr. C 8 % Spectr. D 30 % Spectr. E 7 % Spectr.

toluene (108-88-3) → p-fluorotoluene (352-32-9) + 2-Fluorotoluene (95-52-3) + m-Fluorotoluene (352-70-5) + 2,3,4,6-tetrafluorotoluene

Conditions	Yield
With tetrafluoroammonium tetrafluoroborate In hydrogen fluoride at 0℃; Further byproducts given. Title compound not separated from byproducts;	A 15 % Spectr. B 15 % Spectr. C 8 % Spectr. D 7 % Spectr.

toluene (108-88-3) → p-fluorotoluene (352-32-9) + 2-Fluorotoluene (95-52-3) + benzyl fluoride (350-50-5)

Conditions	Yield
With caesium fluoroxysulphate In acetonitrile at 25℃; Product distribution; Rate constant; reagents ratio, presence of 1,3,5-trinitrobenzene;	A 2 % Chromat. B 4 % Chromat. C 67 % Chromat.
With caesium fluoroxysulphate In acetonitrile Ambient temperature; Yield given. Yields of byproduct given;

2-Fluorotoluene (95-52-3) + carbon dioxide (124-38-9) → 2-fluoro-3-methylbenzoic acid (315-31-1)

Conditions	Yield
Stage #1: 2-Fluorotoluene With sec.-butyllithium In tetrahydrofuran at -78℃; for 0.5h; Stage #2: carbon dioxide In tetrahydrofuran under 760.051 Torr;	100%
Stage #1: 2-Fluorotoluene With n-butyllithium Metallation; Stage #2: carbon dioxide Carboxylation;

benzoimidazole (51-17-2) + 2-Fluorotoluene (95-52-3) → N-(2-methyl-1-phenyl)-1H-benzimidazole (34734-23-1)

Conditions	Yield
With caesium carbonate In N,N-dimethyl acetamide at 210℃; for 12h; Microwave irradiation;	100%

2-Fluorotoluene (95-52-3) → 1-(tert-butyl)-2-fluorobenzene (320-11-6)

Conditions	Yield
With triethanolamine; 2,2'-azobis(isobutyronitrile); chlorine at 90 - 115℃; for 5h;	99%

2-Fluorotoluene (95-52-3) + benzoic acid (65-85-0) → 2-fluorobenzyl benzoate (478970-84-2)

Conditions	Yield
With di-tert-butyl peroxide; C11H23N2(1+)*Br4Fe(1-) at 110℃; for 24h;	98%

2-Fluorotoluene (95-52-3) + phenylmagnesium bromide → 2-methylbiphenyl (643-58-3)

Conditions	Yield
With 1-[2-(diphenylphosphino)phenyl]ethanol; bis(acetylacetonate)nickel(II) In diethyl ether at 20℃; for 5h;	96%
With 1,3-bis(2,6-diisopropylphenyl)-4,5-dihydro-1H-imidazolium tetrafluoroborate; Ni(acac) In tetrahydrofuran at 20℃; for 18h; Kumada-Corriu cross-coupling;	53 % Chromat.

2-Fluorotoluene (95-52-3) + phenylmagnesium bromide (100-58-3) → 2-methylbiphenyl (643-58-3)

Conditions	Yield
Stage #1: 2-Fluorotoluene; phenylmagnesium bromide; 1-[2-(diphenylphosphino)phenyl]ethanol; bis(acetylacetonate)nickel(II) In diethyl ether for 5h; Stage #2: With methanol In diethyl ether Product distribution / selectivity;	96%
Stage #1: 2-Fluorotoluene; phenylmagnesium bromide; bis(acetylacetonate)nickel(II); ((2-hydroxymethyl)phenyl)diphenylphosphine In diethyl ether for 48h; Stage #2: With methanol In diethyl ether Product distribution / selectivity;	95%
With C28H32ClN2NiP In tetrahydrofuran at 20℃; for 24h; Time; Schlenk technique; Inert atmosphere;	16 %Chromat.

2-Fluorotoluene (95-52-3) + 4-dimethylaminophenylmagnesium bromide (7353-91-5) → 2′-methyl-N,N-dimethylbiphenyl-4-amine

Conditions	Yield
With C26H24ClN2NiP*0.1C7H8 In toluene at 25℃; for 24h; Kumada Cross-Coupling; Schlenk technique; Inert atmosphere;	95%

2-Fluorotoluene (95-52-3) + 4-Methylbenzyl chloride (104-82-5) → p-(2-methylbenzyl)toluene (21895-17-0)

Conditions	Yield
With C23H40Br2N2NiO5P; magnesium In tetrahydrofuran at 60℃; for 12h; Inert atmosphere;	95%

2-Fluorotoluene (95-52-3) → 2-Fluorobenzaldehyde (446-52-6)

Conditions	Yield
With Xylaria polymorpha laccase; 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) diammonium salt In 1,4-dioxane at 20℃; for 1.91667h; pH=4.5; Green chemistry; Enzymatic reaction;	94%
With laccase of Pleurotus ostreatus MTCC-1801; 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt In 1,4-dioxane at 20℃; pH=4.5; Enzymatic reaction;	90%
With tert.-butylhydroperoxide; C29H25Cl2N4Ru(1+)*F6P(1-) In acetonitrile at 60℃; for 2h; Schlenk technique; Inert atmosphere;	74%

ammonium hexafluorophosphate + ferrocene (102-54-5) + 2-Fluorotoluene (95-52-3) → η-pentadienyl-η-1,2-fluoromethylbenzeneiron(II) hexafluorophosphate (165681-07-2)

Conditions

Yield

With aluminium trichloride; aluminium In water other Radiation; 0.02 mol metal addn. to arene, Fe- and Al-salts mixt. in 1,2,4-C6H3Cl3 (ratio arene:Fe:AlCl3:Al=2:1:2:1.1), homogenization (stirring), mixt. irradiation in microwave oven (850 W) for 3 min, ice addn. (AlCl3 decompn.), filtration, filtrate washing (Et2O); filtration, treating with aq. NH4-salt, ppt. filtration off through sinter, washing (i-PrOH, Et2O); elem. anal.;

94%

2-Fluorotoluene (95-52-3) + p-methoxybenzyl chloride (824-94-2) → 1-methyl-2-(4-methoxybenzyl) benzene (53039-52-4)

Conditions	Yield
With Ni(PPh3)(1,3-di-tert-butylimidazol-2-ylidene)Br2; magnesium In tetrahydrofuran at 0 - 35℃; for 24h; Schlenk technique; Inert atmosphere;	93%

3-methylamino-1-phenylpropan-1-ol (42142-52-9) + 2-Fluorotoluene (95-52-3) + (S)-Mandelic acid (17199-29-0) → R-(-)-atomoxetine-S-(+)-mandelate

Conditions	Yield
Stage #1: 3-methylamino-1-phenylpropan-1-ol With potassium hydroxide In Triethylene glycol dimethyl ether; toluene at 20 - 120℃; for 1h; Large scale; Stage #2: 2-Fluorotoluene In Triethylene glycol dimethyl ether; toluene for 3h; Large scale; Stage #3: (S)-Mandelic acid at 20 - 75℃; for 1h; Temperature; Large scale;	93%

4-nitro-phenol (100-02-7) + 2-Fluorotoluene (95-52-3) → C13H10FNO2

Conditions	Yield
With di-tert-butyl peroxide; 1,3-di-tert-butylimidazolium at 130℃; for 24h; Green chemistry;	93%

4-nitro-phenol (100-02-7) + 2-Fluorotoluene (95-52-3) → 1-fluoro-2-((4-nitrophenoxy)methyl)benzene (891-75-8)

Conditions	Yield
With di-tert-butyl peroxide; 1,3-di-tert-butylimidazolium at 130℃; for 24h;	93%

2-Fluorotoluene (95-52-3) → (+/-)-atomoxetine (63940-51-2)

Conditions	Yield
Stage #1: 3-methylamino-1-phenylpropan-1-ol With potassium hydroxide In dimethyl sulfoxide at 110℃; Stage #2: 2-Fluorotoluene In dimethyl sulfoxide at 145 - 147℃; for 1h; Heating / reflux;	92.7%

2-Fluorotoluene (95-52-3) + 4-methoxyphenyl magnesium bromide (13139-86-1) → 4'-methoxy-2-methylbiphenyl (92495-54-0)

Conditions	Yield
Stage #1: 2-Fluorotoluene With Ni(PPh3)(1,3-di-tert-butylimidazol-2-ylidene)Br2 In tetrahydrofuran at 0℃; for 0.0333333h; Inert atmosphere; Schlenk technique; Stage #2: 4-methoxyphenyl magnesium bromide In tetrahydrofuran at 0 - 25℃; for 10h; Inert atmosphere; Schlenk technique;	92%
With palladium diacetate; DavePhos In 1,2-dimethoxyethane at 80℃; for 12h;	73%

2-Fluorotoluene (95-52-3) + carbon dioxide (124-38-9) → ortho-methylbenzoic acid (118-90-1)

Conditions	Yield
Stage #1: 2-Fluorotoluene With C78H70Al2Cl4N6P4Rh2; magnesium; ethylene dibromide In tetrahydrofuran at 20℃; for 22h; Inert atmosphere; Glovebox; Stage #2: carbon dioxide In tetrahydrofuran at 20℃; under 760.051 Torr; for 0.5h;	92%

2-Fluorotoluene (95-52-3) + acetyl chloride (75-36-5) → 1-(4-fluoro-3-methylphenyl)ethanone (369-32-4)

Conditions	Yield
With aluminum (III) chloride In chloroform at -5 - 20℃; for 2h; Solvent; Reagent/catalyst; Temperature;	91%
With aluminium trichloride In dichloromethane at 20℃; for 24h; Friedel-Krafts reaction;	82%
With aluminium trichloride
Stage #1: 2-Fluorotoluene; acetyl chloride With aluminum (III) chloride In dichloromethane at 20℃; for 26h; Reflux; Stage #2: With water; sodium carbonate In dichloromethane
With aluminum (III) chloride In dichloromethane at 20℃; for 26h; Reflux;

2-Fluorotoluene (95-52-3) + benzonitrile (100-47-0) → 2-phenyl-indole (948-65-2)

Conditions	Yield
With cesium fluoride; lithium hexamethyldisilazane at 110℃; for 12h; Reagent/catalyst; Temperature; Green chemistry;	90%
With cesium fluoride; lithium hexamethyldisilazane at 110℃; for 12h; Reagent/catalyst; Concentration; Sealed tube; Inert atmosphere;	90%

2-Fluorotoluene (95-52-3) + (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8) → (R)-tomoxetine (105314-52-1, 105314-53-2, 63940-51-2, 83015-26-3)

Conditions	Yield
Stage #1: (R)-N-methyl-3-phenyl-3-hydroxypropylamine With potassium hydroxide In dimethyl sulfoxide at 130℃; for 1h; Stage #2: 2-Fluorotoluene In dimethyl sulfoxide at 130℃;	89.51%
Stage #1: (R)-N-methyl-3-phenyl-3-hydroxypropylamine With sodium hydride In dimethyl sulfoxide for 0.25h; Stage #2: With Potassium benzoate In dimethyl sulfoxide at 50 - 55℃; for 1h; Stage #3: 2-Fluorotoluene In dimethyl sulfoxide at 50 - 120℃; for 6.25 - 7.25h;
With potassium tert-butylate In dimethyl sulfoxide at 60℃; for 8h;

2-Fluorotoluene (95-52-3) + 4-tert-butyl benzonitrile (4210-32-6) → 2-(4-(tert-butyl)phenyl)-1H-indole (521295-49-8)

Conditions	Yield
With cesium fluoride; lithium hexamethyldisilazane at 110℃; for 12h; Sealed tube; Inert atmosphere;	89%

2-Fluorotoluene (95-52-3) → 5-nitro-2-fluorotoluene (455-88-9)

Conditions	Yield
With 2C2H3F3O*BF3; potassium nitrate at 20℃; for 5h;	88%
With nitric acid
With nitric acid; Nitrogen dioxide
With nitric acid

2-Fluorotoluene (95-52-3) + C15H25AlO → 4'-methoxy-2-methylbiphenyl (92495-54-0)

Conditions	Yield
With bis(tricyclohexylphosphine)nickel(II) dichloride In tetrahydrofuran at 50℃; for 24h; Inert atmosphere;	88%

cyclopentadienylruthenium(II) trisacetonitrile hexafluorophosphate + 2-Fluorotoluene (95-52-3) → C12H12FRu(1+)*F6P(1-)

Conditions	Yield
In 1,2-dichloro-ethane at 90℃; for 18h; Inert atmosphere;	88%

2-Fluorotoluene (95-52-3) + (E)-N-(2-(4-methoxyphenyl)propan-2-yl)-1-phenylmethanimine → N-(2-(2-fluorophenyl)-1-phenylethyl)-2-(4-methoxyphenyl)propan-2-amine

Conditions	Yield
With potassium tert-butylate; 2,2,6,6-tetramethylpiperidinyl-lithium at -40℃; for 18h; Glovebox; Inert atmosphere;	88%

2-naphthalenecarbonitrile (613-46-7) + 2-Fluorotoluene (95-52-3) → 2-(2-naphthyl)indole (23746-81-8)

Conditions	Yield
With cesium fluoride; lithium hexamethyldisilazane In 1,4-dioxane at 110℃; for 12h; Green chemistry;	88%
With cesium fluoride; lithium hexamethyldisilazane In 1,2-dimethoxyethane at 110℃; for 12h; Solvent; Sealed tube; Inert atmosphere;	88%

2-Fluorotoluene (95-52-3) + bis(pinacol)diborane (73183-34-3) → 2-methylphenylboronic acid pinacol ester (195062-59-0)

Conditions	Yield
With bis(1,5-cyclooctadiene)nickel (0); copper(l) iodide; cesium fluoride; tricyclohexylphosphine In toluene at 80℃; for 24h; Inert atmosphere;	87.6%
With chlorobis(tricyclohexylphosphine)copper(I); cesium fluoride In toluene at 80℃; for 24h;	79%
With tetramethylammonium fluoride; 2-mercaptopyridine sodium salt In acetonitrile at 30 - 35℃; for 24h; Irradiation; Inert atmosphere;	57%

2-Fluorotoluene (95-52-3) + C19H13CrO3 → (η6-1-fluoro-2-methylbenzene)tricarbonylchromium(0) (32913-59-0)

Conditions	Yield
In 1,4-dioxane at 90℃; for 16h;	86%

Upstream product

• 462-06-6 fluorobenzene 
• 593-53-3 Methyl fluoride 
• 56-23-5 tetrachloromethane 
• 108-88-3 toluene 
• 107-31-3 Methyl formate 
• 138850-94-9 C₇H₇F*H⁽¹⁺⁾ 
• 95-53-4 o-toluidine 
• 615-37-2 ortho-methylphenyl iodide 
• 546-67-8 lead(IV) tetraacetate 
• 109-63-7 trifluoroborane diethyl ether 
• 108-41-8 1-chloro-3-methylbenzene 
• 95-49-8 2-methylchlorobenzene 
• 106-43-4 para-chlorotoluene 
• 446-48-0 o-fluorobenzyl bromide 

Downstream Products

• 342-46-1 2-(3-fluoro-4-methyl-benzoyl)-benzoic acid 
• 446-48-0 o-fluorobenzyl bromide 
• 452-66-4 5-chloro-2-fluorotoluene 
• 443-83-4 2-chloro-6-fluorotoluene 
• 455-88-9 5-nitro-2-fluorotoluene 
• 769-10-8 1-fluoro-2-methyl-3-nitrobenzene 
• 349-38-2 1,2-bis(2-fluorophenyl)ethane 
• 320-65-0 ortho-fluoro-benzal chloride 
• 348-97-0 2-fluoro-3,5-dinitro-toluene 
• 488-98-2 α,α,α-trichloro-2-fluorotoluene 
• 315-31-1 2-fluoro-3-methylbenzoic acid 
• 629672-19-1 4-fluoro-3-methylbenzene-1-sulfonyl chloride 
• 345-35-7 2-fluorobenzyl chloride 
• 446-52-6 2-Fluorobenzaldehyde 

Relevant articles and documents

Full continuous flow synthesis process of fluorine-containing aromatic hydrocarbon compounds

The invention provides a full continuous flow synthesis process of a fluorine-containing aromatic hydrocarbon compound, and belongs to the technical field of preparation of halogenated hydrocarbon carbocyclic organic compounds. Arylamine and hydrogen fluoride are pumped into a thermostat A and a thermostat B respectively and flow into a micro-channel reactor C for a salt forming reaction after constant temperature treatment, and a sulfuric acid solution of nitrosyl sulfuric acid is pumped into a thermostat D and flows into a micro-channel reactor E together with a salt forming product flowing out of the micro-channel reactor C for a diazotization reaction after constant temperature treatment. A product flows into a micro-channel reactor F to be subjected to a thermal decomposition reaction, is cooled by a cooler G and then enters a three-phase separator H to be continuously separated, nitrogen is discharged after being subjected to spraying deacidification, a fluorine-containing aromatic hydrocarbon crude product is subjected to continuous alkali washing, continuous drying and continuous rectification to obtain a fluorine-containing aromatic hydrocarbon finished product, and a hydrofluoric acid and sulfuric acid mixture is subjected to continuous distillation to obtain a product. The hydrogen fluoride and sulfuric acid are obtained. The full continuous flow synthesis process has the advantages of high reaction yield, excellent product quality, good production safety, less pollutant discharge and the like.

Fluorination of arylboronic esters enabled by bismuth redox catalysis

Bismuth catalysis has traditionally relied on the Lewis acidic properties of the element in a fixed oxidation state. In this paper, we report a series of bismuth complexes that can undergo oxidative addition, reductive elimination, and transmetallation in a manner akin to transition metals. Rational ligand optimization featuring a sulfoximine moiety produced an active catalyst for the fluorination of aryl boronic esters through a bismuth (III)/bismuth (V) redox cycle. Crystallographic characterization of the different bismuth species involved, together with a mechanistic investigation of the carbonfluorine bond-forming event, identified the crucial features that were combined to implement the full catalytic cycle.

Mechanochemical Activation of Zinc and Application to Negishi Cross-Coupling

A form independent activation of zinc, concomitant generation of organozinc species and engagement in a Negishi cross-coupling reaction via mechanochemical methods is reported. The reported method exhibits a broad substrate scope for both C(sp3)–C(sp2) and C(sp2)–C(sp2) couplings and is tolerant to many important functional groups. The method may offer broad reaching opportunities for the in situ generation organometallic compounds from base metals and their concomitant engagement in synthetic reactions via mechanochemical methods.