1422-53-3

Basic information

• Product Name: 2-Bromo-4-fluorotoluene
• Synonyms: 2-BROMO-4-FLUOROTOLUENE MIN 99%;2-Bromo-4-flurotoluene;2-Bromo-4-fluorotoluene, 98+%;2-Bromo-4-fluorotoluene,97%;2-Bromo-4-fluorotolu;2 - broMine - 4 - fluorine toluene;2-BROMO-4-FLUOROTOLUENE;2-BROMO-4-FLUORO-1-METHYLBENZENE
• CAS NO: 1422-53-3
• Molecular Formula: C₇H₆BrF
• Molecular Weight: 189.02
• EINECS: 215-830-0
• Product Categories: Aromatic Halides (substituted);Halogen toluene;Miscellaneous;Bromine Compounds;Fluorine Compounds;Aryl;C7;Halogenated Hydrocarbons;Aryl Fluorinated Building Blocks;Building Blocks;Chemical Synthesis;Fluorinated Building Blocks;Halogenated Hydrocarbons;Organic Building Blocks;Organic Fluorinated Building Blocks;Other Fluorinated Organic Building Blocks;Indazoles;Fluorin-contained toluene series
• Mol File: 1422-53-3.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 170-172 °C(lit.)
• Flash Point: 148 °F
• Appearance: colorless or yellowish liquid
• Density: 1.526 g/mL at 25 °C(lit.)
• Vapor Pressure: 1.23mmHg at 25°C
• Refractive Index: n20/D 1.528(lit.)
• Storage Temp.: Room temperature.
• BRN: 1859038
• CAS DataBase Reference: 2-Bromo-4-fluorotoluene(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Bromo-4-fluorotoluene(1422-53-3)
• EPA Substance Registry System: 2-Bromo-4-fluorotoluene(1422-53-3)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36/37/39-37/39
• RIDADR: UN 2810
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 1422-53-3(Hazardous Substances Data)

Usage

Chemical Properties

colorless to light yellow liquid

Uses

2-Bromo-4-fluorotoluene may be used in the preparation of meta-fluoro analog, (tris(5-fluoro-2-methylphenyl)phosphane, F-TOTP).

InChI:InChI=1/C7H6BrF/c1-5-6(8)3-2-4-7(5)9/h2-4H,1H3

Synthetic route

3-bromo-4-methylaniline (7745-91-7) → 2-bromo-4-fluorotoluene (1422-53-3)

Conditions	Yield
(i) NaNO2, aq. HCl, aq. HBF4, (ii) (pyrolysis); Multistep reaction;

2-bromo-4-fluorotoluene (1422-53-3) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → 2-bromo-6-fluoro-3-methylbenzaldehyde

Conditions	Yield
Stage #1: 2-bromo-4-fluorotoluene With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 2h; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran at 20℃; for 0.5h; Reagent/catalyst; Temperature;	92%
Stage #1: 2-bromo-4-fluorotoluene With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1h; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran at 20℃; for 1h;	91.3%
Stage #1: 2-bromo-4-fluorotoluene With n-butyllithium; diisopropylamine In tetrahydrofuran at -78℃; for 2.16667h; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran at -78℃; for 0.333333h;	84%

2-bromo-4-fluorotoluene (1422-53-3) + 2,3-Dimethylaniline (87-59-2) → 5-fluoro-2,2',3'-trimethyl-diphenylamine (917241-99-7)

Conditions	Yield
With sodium t-butanolate; palladium diacetate; 2'-dicyclohexylphosphanyl-6-hydroxy-biphenyl-3-sulfonic acid In diethylene glycol dimethyl ether at 120℃; for 15h; Product distribution / selectivity;	90%

2-bromo-4-fluorotoluene (1422-53-3) + tert butyl 4-formylpiperidine-1-carboxylate (137076-22-3) → tert-butyl 4-(5-fluoro-2-methylbenzoyl)piperidine-1-carboxylate

Conditions	Yield
With Quinuclidine; [nickel(II) (4,4'-di-tert-butyl-2,2'-bipyridine)(bromide)2]; [Ir(C6H2F2-C5H3NCF3)2(4,4′-di-tert-butyl-2,2′-dipyridyl)]; potassium carbonate In 1,4-dioxane at 20℃; for 20h; Inert atmosphere; Sealed tube; Irradiation;	90%

2-bromo-4-fluorotoluene (1422-53-3) + 1-chloro-1-methylsiletane (2351-34-0) → 1-(2-bromo-6-fluoro-3-methylphenyl)-1-methylsiletane

Conditions	Yield
With lithium diisopropyl amide In tetrahydrofuran at -78 - 20℃; Inert atmosphere; Schlenk technique;	90%

methyl(tetramethylene)silyl chloride (2406-31-7) + 2-bromo-4-fluorotoluene (1422-53-3) → 1-(2-bromo-6-fluoro-3-methylphenyl)-1-methylsilolane

Conditions	Yield
With lithium diisopropyl amide In tetrahydrofuran at -78 - 20℃; Inert atmosphere; Schlenk technique;	90%

2-bromo-4-fluorotoluene (1422-53-3) + (1-acetylpiperidin-4-yl)acetic acid (78056-60-7) → 2-(1-acetylpiperidin-4-yl)-1-(4-bromo-2-fluoro-5-methylphenyl)ethan-1-one

Conditions	Yield
Stage #1: (1-acetylpiperidin-4-yl)acetic acid With thionyl chloride at 20℃; Stage #2: 2-bromo-4-fluorotoluene With aluminum (III) chloride at 80℃; for 2h;	88%

2-bromo-4-fluorotoluene (1422-53-3) → 2-bromo-4-fluorobenzyl bromide (61150-57-0)

Conditions	Yield
With N-Bromosuccinimide; dibenzoyl peroxide In tetrachloromethane at 70℃; for 18h;	87%
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) In tetrachloromethane for 21h; Heating / reflux;	87%
With N-Bromosuccinimide; dibenzoyl peroxide In tetrachloromethane for 2h; Heating / reflux;	76%

2-bromo-4-fluorotoluene (1422-53-3) + phenylboronic acid (98-80-6) → 3-fluoro-6-methylbiphenyl (939771-54-7)

Conditions	Yield
With potassium carbonate; tetrakis(triphenylphosphine) palladium(0) In 1,2-dimethoxyethane at 80 - 120℃; for 0.666667h; Microwave irradiation;	86%
With potassium carbonate; tetrakis(triphenylphosphine) palladium(0) In 1,2-dimethoxyethane at 80 - 120℃; for 0.666667h; Microwave;	86%

2-bromo-4-fluorotoluene (1422-53-3) + carbon dioxide (124-38-9) → 2-bromo-6-fluoro-3-methylbenzoic acid (1359857-60-5)

Conditions	Yield
Stage #1: 2-bromo-4-fluorotoluene With n-butyllithium; diisopropylamine In tetrahydrofuran Cooling with ice; Stage #2: carbon dioxide In tetrahydrofuran for 0.333333h; Cooling with ice;	85%

2-bromo-4-fluorotoluene (1422-53-3) → tris(5-fluoro-2-methylphenyl)phosphane

Conditions	Yield
Stage #1: 2-bromo-4-fluorotoluene With magnesium In tetrahydrofuran at 20 - 75℃; Stage #2: With phosphorus trichloride In tetrahydrofuran for 1h; Heating;	82%

2-bromo-4-fluorotoluene (1422-53-3) → 2-bromo-4-fluorobenzoic acid (1006-41-3)

Conditions	Yield
With carbon tetrabromide; oxygen In acetonitrile at 20℃; for 60h; Irradiation;	79%
With carbon tetrabromide; oxygen In acetonitrile at 20℃; for 60h; UV-irradiation;	78.5%
With 2,2'-azobis(isobutyronitrile); oxygen; cobalt(II) diacetate tetrahydrate; acetic acid; sodium bromide at 130℃; under 9000.9 Torr; for 1.5h; Green chemistry;	41%
With potassium permanganate; magnesium sulfate
With oxygen; cobalt(III) acetate

cis-dichlorobis(triphenylphosphine)platinum(II) (10199-34-5, 14056-88-3, 15604-36-1) + 2-bromo-4-fluorotoluene (1422-53-3) → cis-bis(2-methyl-5-fluorophenyl)bis(triphenylphosphane)platinum(II)

Conditions	Yield
With n-butyl lithium In diethyl ether byproducts: LiCl; formation of Li-aryl compd. from BuLi and aryl compd. (room temp., 1 h), addn. of Pt complex in one portion to Li compd. soln. under inert gas, room temp.; stirring, 20°C, 0.5 h; hydrolysis of excess of Li compd. by ice-water; filtration; chromy. (silica gel, CH2Cl2); elem. anal.;	77%

2-bromo-4-fluorotoluene (1422-53-3) + N-cyano-N-phenyl-p-toluenesulfonamide (55305-43-6) → 3-fluoro-6-methylbenzonitrile (77532-79-7)

Conditions	Yield
Stage #1: 2-bromo-4-fluorotoluene With magnesium; lithium chloride In tetrahydrofuran at 20℃; Inert atmosphere; Stage #2: N-cyano-N-phenyl-p-toluenesulfonamide In tetrahydrofuran at 0 - 20℃; Inert atmosphere;	77%

2-bromo-4-fluorotoluene (1422-53-3) + formic acid ethyl ester (109-94-4) → 2-bromo-6-fluoro-3-methylbenzaldehyde

Conditions	Yield
Stage #1: 2-bromo-4-fluorotoluene With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1.5h; Stage #2: formic acid ethyl ester In tetrahydrofuran at -78℃; for 0.0833333h;	76.9%

2-bromo-4-fluorotoluene (1422-53-3) + (2,6-dimethoxyphenyl)boronic acid (23112-96-1) → 5-fluoro-2',6'-dimethoxy-2-methylbiphenyl (1267964-65-7)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In ethanol; water; toluene for 18h; Suzuki-Miyaura cross-coupling; Inert atmosphere; Reflux;	76%

2-bromo-4-fluorotoluene (1422-53-3) → 3-fluoro-6-methylaniline (367-29-3)

Conditions	Yield
With ammonium sulfate; (R)-(-)-1-[(SP)-2-(dicyclohexylphosphino)ferrocenyl]ethyldi-tert-butylphosphine; bis(tri-ortho-tolylphosphine)palladium(0); sodium t-butanolate In 1,4-dioxane at 100℃; for 8h; Inert atmosphere; Glovebox;	76%

2-bromo-4-fluorotoluene (1422-53-3) + anthranil (271-58-9) → C14H10FNO

Conditions	Yield
With potassium acetate In N,N-dimethyl acetamide at 150℃; for 20h; Inert atmosphere;	60%

2-bromo-4-fluorotoluene (1422-53-3) → 1-bromo-2-methyl-4-nitro-5-fluorobenzene (64695-96-1)

Conditions	Yield
With sulfuric acid; potassium nitrate at 0 - 25℃; for 2h; Inert atmosphere;	54.3%
With nitric acid; Nitrogen dioxide
With potassium nitrite; sulfuric acid In water at 0 - 25℃; for 15.75h;

5-phenylimidazo[2,1-b][1,3,4]thiadiazole (25752-18-5) + 2-bromo-4-fluorotoluene (1422-53-3) → 2-((5-fluoro-2-methylphenyl)thio)-4-phenyl-1H-imidazole

Conditions	Yield
With copper acetylacetonate; potassium carbonate In 1-methyl-pyrrolidin-2-one at 140℃; for 2h; Microwave irradiation;	53%

trifluoroacetonitrile (353-85-5) + 2-bromo-4-fluorotoluene (1422-53-3) → 2-(5-fluoro-2-methylphenyl)-2,4,6-tris(trifluoromethyl)-1,2-dihydro-1,3,5-triazine + 2,2,2-trifluoro-1-(5-fluoro-2-methylphenyl)ethanimine

Conditions	Yield
Stage #1: 2-bromo-4-fluorotoluene With magnesium In diethyl ether Stage #2: trifluoroacetonitrile In diethyl ether Further stages.;	A 23% B 49%

1-phenylmethyl-4-piperidone (3612-20-2) + hexane-EtOAc + 2-bromo-4-fluorotoluene (1422-53-3) → 1-benzyl-4-(4-fluoro-2-methylphenyl)piperidin-4-ol (216311-09-0)

Conditions	Yield
With n-butyllithium In tetrahydrofuran	46%

2-bromo-4-fluorotoluene (1422-53-3) → 2-bromo-4-fluorobenzaldehyde (59142-68-6)

Conditions	Yield
Stage #1: 2-bromo-4-fluorotoluene With N-Bromosuccinimide; dibenzoyl peroxide In ethyl acetate at 80℃; for 1h; Stage #2: With hexamethylenetetramine In water; acetic acid at 100℃; for 1h; Stage #3: With hydrogenchloride In water for 1h;	41%
With chromium(VI) oxide; acetic anhydride

(E)-2,7-dimethyl-2,6-octadienal (72172-57-7) + 2-bromo-4-fluorotoluene (1422-53-3) → (E)-4-(5-fluoro-2-methylphenyl)-2,7-dimethylocta-2,6-dienal

Conditions	Yield
With palladium diacetate; caesium carbonate; tricyclohexylphosphine In N,N-dimethyl-formamide at 110 - 120℃; Inert atmosphere;	28%

t-butylnitrite (917-95-3) + 2-bromo-4-fluorotoluene (1422-53-3) → N-tert-Butyl-N-(5-fluoro-2-methyl-phenyl)-hydroxylamine (53104-10-2)

Conditions	Yield
(i) Mg, BrCH2CH2Br, (ii) /BRN= 1737613/; Multistep reaction;

2-bromo-4-fluorotoluene (1422-53-3) → 3-Brom-4-methyl-2.6-dinitrophenol (64695-95-0)

Conditions	Yield
(i) NO2/HNO3, (ii) aq. NaOH, CHCl3; Multistep reaction;

2-bromo-4-fluorotoluene (1422-53-3) + ethyl acrylate (140-88-5) → Ethyl 3-(5'-fluoro-2'-methylphenyl)propanoate (137466-12-7)

Conditions	Yield
With magnesium; copper(l) chloride 1.) diethyl ether, reflux, 2h, 2.) -17 deg C; Yield given. Multistep reaction;

2-bromo-4-fluorotoluene (1422-53-3) + succinic acid monomethylester chloride (1490-25-1) → methyl 3-(5-fluoro-2-methylbenzoyl)propionate (97072-91-8)

Conditions	Yield
With magnesium; cadmium(II) chloride 1.) diethyl ether; 2.) benzene, Et2O, 45 min, reflux; 3.) benzene, reflux, 1.5 h; overnight, RT; Yield given. Multistep reaction;

2-bromo-4-fluorotoluene (1422-53-3) → 4-bromo-6-fluoro-2,3-dihydro-1H-inden-1-one (174603-56-6)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: 62 percent / N-bromosuccinimide; benzoyl peroxide / CCl4 / 18 h / Heating; IR illumination 2.1: sodium hydride / 1,2-dimethoxy-ethane / 1 h / 20 °C 2.2: 40 percent / 1,2-dimethoxy-ethane / 1.5 h / Heating 3.1: aq. KOH / 4.5 h / Heating 3.2: 91 percent / aq. H2SO4 / 18 h / Heating 4.1: oxalyl chloride / CH2Cl2 / 18 h / 20 °C 5.1: aluminum chloride / CH2Cl2 / 2 h / Heating View Scheme

2-bromo-4-fluorotoluene (1422-53-3) → 3-(2-bromo-4-fluorophenyl)propionyl chloride

Conditions	Yield
Multi-step reaction with 4 steps 1.1: 62 percent / N-bromosuccinimide; benzoyl peroxide / CCl4 / 18 h / Heating; IR illumination 2.1: sodium hydride / 1,2-dimethoxy-ethane / 1 h / 20 °C 2.2: 40 percent / 1,2-dimethoxy-ethane / 1.5 h / Heating 3.1: aq. KOH / 4.5 h / Heating 3.2: 91 percent / aq. H2SO4 / 18 h / Heating 4.1: oxalyl chloride / CH2Cl2 / 18 h / 20 °C View Scheme

Upstream product

• 7745-91-7 3-bromo-4-methylaniline 

Downstream Products

• 367-29-3 3-fluoro-6-methylaniline 
• 1027564-90-4 1,1,1-trifluoro-4-(5-fluoro-2-methylphenyl)-2-(5-isopropoxy-1H-pyrrolo[2,3-c] pyridin-2-ylmethyl)-4-methylpentan-2-ol 
• 1027986-11-3 1,1,1-trifluoro-4-(5-fluoro-2-methylphenyl)-4-methyl-2-(5-morpholin-4-yl-1H-pyrrolo[2,3-c] pyridin-2-ylmethyl) pentan-2-ol 
• 609851-95-8 1,1,1-trifluoro-4-(5-fluoro-2-methylphenyl)-4-methyl-2-(1H-pyrrolo[2,3-c]pyridin-2-ylmethyl)pentan-2-ol 
• 875415-00-2 1,1,1-trifluoro-(5-fluoro-2-methylphenyl)-4-methyl-2-(3-methyl-1H-pyrrolo[2,3-c] pyridin-2-ylmethyl) pentan-2-ol 
• 1346984-80-2 C₂₂H₂₄F₄N₂O 
• 849354-28-5 6-(5-fluoro-2-methylphenyl)-6-methyl-4-trifluoromethylhept-1-yn-4-ol 
• 1260095-04-2 {4-[6-(5-fluoro-2-methylphenyl)-4-hydroxy-6-methyl-4-trifluoromethylhept-1-ynyl]pyridin-3-yl}carbamic acid tert-butyl ester 

Relevant articles and documents

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