452-74-4

Basic information

• Product Name: 4-Bromo-3-fluorotoluene
• Synonyms: 3-FLUORO-4-BROMO-TOLUENE;4-BROMO-3-FLUOROTOLUENE;4-Bromo-3-fluorotoluene,98+%;4-Bromo-3-fluorotoluene 98%;4-Bromo-3-fluoro-1-methylbenzene;4-Bromo-3-flurotoluene;3-FLUORO-4-BROMO-TOLUONE;4-BroMo-3-fluorotoluene, 98% 5GR
• CAS NO: 452-74-4
• Molecular Formula: C₇H₆BrF
• Molecular Weight: 189.02
• EINECS: -0
• Product Categories: Fluorin-contained toluene series;blocks;Bromides;FluoroCompounds;Aromatic Halides (substituted);Halogen toluene;Miscellaneous;Bromine Compounds;Fluorine Compounds;Aryl;C7;Halogenated Hydrocarbons
• Mol File: 452-74-4.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 95 °C50 mm Hg(lit.)
• Flash Point: 95 °F
• Appearance: Clear light yellow/Liquid
• Density: 1.494 g/mL at 25 °C(lit.)
• Refractive Index: n20/D 1.53(lit.)
• Storage Temp.: Flammables area
• BRN: 2500154
• CAS DataBase Reference: 4-Bromo-3-fluorotoluene(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Bromo-3-fluorotoluene(452-74-4)
• EPA Substance Registry System: 4-Bromo-3-fluorotoluene(452-74-4)

Safety Data

• Hazard Codes: Xi
• Statements: 10-36/37/38
• Safety Statements: 26-37/39-16
• RIDADR: UN 1993 3/PG 3
• WGK Germany: 3
• HazardClass: 3
• PackingGroup: III
• Hazardous Substances Data: 452-74-4(Hazardous Substances Data)

Usage

Chemical Properties

colorless to light yellow liqui

Uses

Different sources of media describe the Uses of 452-74-4 differently. You can refer to the following data:
1. 4-Bromo-3-fluorotoluene is used in the synthesis of S-trityl-L-cysteine based inhibitors that show potent antitumor activity in lung cancer models. Chemical reagent for organic synthesis.
2. 4-Bromo-3-fluorotoluene may be used in the preparation of 1-(4-cyano-3- fluorobenzyl)-5-imidazolecarboxaldehyde and 1-bromo-4-bromomethyl-2-fluorobenzene.

General Description

4-Bromo-3-fluorotoluene (1-bromo-2-fluoro-4-methylbenzene) is an aryl fluorinated building block. Synthesis of 4-bromo-3-fluorotoluene from o-nitro-p-toluidine (Fast Red Base GL), via diazo reaction at high temperature, Sandmeyer reaction, reduction and Schiemann reaction has been reported. Its density and refractive index have been determined.

Synthetic route

2,6-dibromo-3-fluorotoluene + 2,4-dibromo-5-fluorotoluene (93765-84-5) → 4-bromo-3-fluorotoluene (452-74-4)

Conditions	Yield
With 5%-palladium/activated carbon; hydrogen; sodium acetate In methanol at 75 - 80℃; under 16501.7 Torr; for 10h; Pressure; Solvent; Temperature; Autoclave;	92%

2-bromo-5-methylaniline (53078-85-6) → 4-bromo-3-fluorotoluene (452-74-4)

Conditions	Yield
Stage #1: 2-bromo-5-methylaniline With hydrogenchloride; sodium tetrafluoroborate; sodium nitrite Stage #2: Schiemann reaction; Heating;	57.7%

m-Fluorotoluene (352-70-5) → 2-Bromo-5-fluorotoluene (452-63-1) + 4-bromo-3-fluorotoluene (452-74-4)

Conditions	Yield
With tetrachloromethane; iron Bromierung;

4-methyl-2-nitroaniline (89-62-3) → 4-bromo-3-fluorotoluene (452-74-4)

Conditions	Yield
Multistep reaction;

2-bromo-5-methyl benzenediazonium tetrafluoroborate → 4-bromo-3-fluorotoluene (452-74-4)

Conditions	Yield
(heating);

tetrachloromethane (56-23-5) + m-Fluorotoluene (352-70-5) + bromine (7726-95-6) + iron-powder → 2-Bromo-5-fluorotoluene (452-63-1) + 4-bromo-3-fluorotoluene (452-74-4)

m-Fluorotoluene (352-70-5) → 4-bromo-3-fluorotoluene (452-74-4) + 5-fluoro-2-bromo-1-methyl-benzene

Conditions	Yield
With tetrachloromethane; iron Bromierung;

4-Bromo-3-nitrotoluene (5326-34-1) → 4-bromo-3-fluorotoluene (452-74-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 84.9 percent / Fe; CH3COOH 2.1: HCl; NaBF4; NaNO2 2.2: 57.7 percent / Heating View Scheme

4-methyl-2-nitroacetanilide (612-45-3) → 4-bromo-3-fluorotoluene (452-74-4)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: 99.4 percent / Claisen's base 2.1: H2SO4; NaNO2 2.2: 51.8 percent / Cu2Br2 3.1: 84.9 percent / Fe; CH3COOH 4.1: HCl; NaBF4; NaNO2 4.2: 57.7 percent / Heating View Scheme

4-methyl-2-nitroaniline (89-62-3) + MCN → 4-bromo-3-fluorotoluene (452-74-4)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: H2SO4; NaNO2 1.2: 51.8 percent / Cu2Br2 2.1: 84.9 percent / Fe; CH3COOH 3.1: HCl; NaBF4; NaNO2 3.2: 57.7 percent / Heating View Scheme

methylmagnesium bromide (75-16-1) + 4-bromo-3-fluoroiodobenzene (136434-77-0) → 4-bromo-3-fluorotoluene (452-74-4)

Conditions	Yield
With C72H63P6Pd3(1+)*I(1-) In tetrahydrofuran; toluene at 20℃; Inert atmosphere; Glovebox; chemoselective reaction;	89 %Spectr.

2-Bromo-5-fluorotoluene (452-63-1) → 4-bromo-3-fluorotoluene (452-74-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: iron; bromine / 1,2-dichloro-ethane / 2.5 h / 30 - 35 °C 2: sodium acetate; 5%-palladium/activated carbon; hydrogen / methanol / 10 h / 75 - 80 °C / 16501.7 Torr / Autoclave View Scheme

m-Fluorotoluene (352-70-5) → 4-bromo-3-fluorotoluene (452-74-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: iron; bromine / 1,2-dichloro-ethane / 10 h / 30 - 35 °C 2: sodium acetate; 5%-palladium/activated carbon; hydrogen / methanol / 10 h / 75 - 80 °C / 16501.7 Torr / Autoclave View Scheme

4-bromo-3-fluorotoluene (452-74-4) + copper(I) cyanide (544-92-3) → 2-fluoro-4-methylbenzonitrile (85070-67-3)

Conditions	Yield
In N,N-dimethyl-formamide for 24h; Heating;	100%
In N,N-dimethyl-formamide for 5h; Heating;	94%
In N,N-dimethyl-formamide for 24h; Heating / reflux;	88%

4-bromo-3-fluorotoluene (452-74-4) → 3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7)

Conditions	Yield
With sulfuric acid; potassium nitrate at 0 - 20℃;	100%
With sulfuric acid; potassium nitrate at 0℃;	100%
With sulfuric acid; nitric acid at 0℃;	92%

carbon monoxide (201230-82-2) + 4-bromo-3-fluorotoluene (452-74-4) + benzamidine monohydrochloride (1670-14-0) → 7-methyl-2-phenylquinazoline-4(3H)-one

Conditions	Yield
With palladium diacetate; N-ethyl-N,N-diisopropylamine; catacxium A In N,N-dimethyl acetamide at 140℃; under 7500.75 Torr; for 22h; Inert atmosphere; Autoclave;	99%

1,3-thiazole (288-47-1) + 4-bromo-3-fluorotoluene (452-74-4) → 5-(2-fluoro-4-methylphenyl)thiazole

Conditions	Yield
With palladium diacetate; potassium carbonate; catacxium A; Trimethylacetic acid In N,N-dimethyl acetamide at 110℃; for 16h; Inert atmosphere;	99%

4-bromo-3-fluorotoluene (452-74-4) → 2-fluoro-4-methylphenylboronic acid (170981-26-7)

Conditions	Yield
	97%
With n-butyllithium; triethyl borate In tetrahydrofuran; hexane at -70 - 20℃; for 19h;	75%
With n-butyllithium; Triisopropyl borate In tetrahydrofuran; hexane; toluene at -40℃; for 2h;

4-bromo-3-fluorotoluene (452-74-4) + dicyanozinc (557-21-1) → 2-fluoro-4-methylbenzonitrile (85070-67-3)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0) In N,N-dimethyl-formamide at 80℃;	96%
tetrakis(triphenylphosphine) palladium(0) In N,N-dimethyl-formamide at 80℃; for 3h;	96%

trifluoroethylamine (753-90-2) + 4-bromo-3-fluorotoluene (452-74-4) → C9H9F4N

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;	96%

benzoimidazole (51-17-2) + 4-bromo-3-fluorotoluene (452-74-4) → 1-(2-bromo-5-methylphenyl)benzimidazole

Conditions	Yield
With potassium phosphate In N,N-dimethyl-formamide at 150℃;	96%

4-bromo-3-fluorotoluene (452-74-4) → 4-bromo-3-fluorobenzoic acid (153556-42-4)

Conditions	Yield
With pyridine; potassium permanganate for 40h; Heating;	94%
With pyridine; potassium permanganate at 90℃;	88%
Stage #1: 4-bromo-3-fluorotoluene With pyridine; potassium permanganate; water at 90℃; for 3h; Stage #2: With sodium hydroxide In water Stage #3: With hydrogenchloride In water pH=2;	73%

4-bromo-3-fluorotoluene (452-74-4) + sodium cyanoacetate (1071-36-9) → 2-(2-fluoro-4-methylphenyl)acetonitrile (518070-26-3)

Conditions	Yield
With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; bis(η3-allyl-μ-chloropalladium(II)) In 1,3,5-trimethyl-benzene at 20 - 140℃; for 5.16667h; Inert atmosphere; Sealed tube; chemoselective reaction;	91%

4-bromo-3-fluorotoluene (452-74-4) → 1-bromo-4-(bromomethyl)-2-fluorobenzene (127425-73-4)

Conditions	Yield
With N-Bromosuccinimide; dibenzoyl peroxide In acetonitrile for 3h; Reflux;	90%
With N-Bromosuccinimide; dibenzoyl peroxide In acetonitrile for 3h; Reflux;	90%
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) In tetrachloromethane for 3.5h; Reflux;	80%

4-bromo-3-fluorotoluene (452-74-4) + bis(pinacol)diborane (73183-34-3) → 2-(2-fluoro-4-methylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1165936-03-7)

Conditions	Yield
With bis[di-t-butyl(p-dimethylaminophenyl)phosphino]palladium (II) Dichloride; potassium propionate In ethyl acetate Suzuki Coupling; Reflux;	90%
With 10H-phenothiazine; caesium carbonate In acetonitrile for 24h; Irradiation; Sealed tube; Inert atmosphere;	65%
With potassium acetate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride In DMF (N,N-dimethyl-formamide) at 20 - 80℃; for 16h;

carbon monoxide (201230-82-2) + 4-bromo-3-fluorotoluene (452-74-4) + 2-Hydroxy-4-methylanilin (2835-98-5) → 3,7-dimethyldibenzo[b,f][1,4]oxazepin-11(10H)-one

Conditions	Yield
With palladium diacetate; 1,8-diazabicyclo[5.4.0]undec-7-ene; catacxium A In dimethyl sulfoxide at 120℃; for 24h;	87%

4-bromo-3-fluorotoluene (452-74-4) + 3,4-dichlophenylboronic acid (151169-75-4) → 3',4'-dichloro-2-fluoro-4-methyl-biphenyl (1200722-42-4)

Conditions	Yield
With sodium carbonate; palladium 10% on activated carbon In ethanol for 4h; Suzuki Coupling; Reflux; Inert atmosphere;	86%

carbon monoxide (201230-82-2) + 2-amino-4-fluorophenol (399-97-3) + 4-bromo-3-fluorotoluene (452-74-4) → 8-fluoro-3-methyldibenzo[b,f][1,4]oxazepin-11(10H)-one

Conditions	Yield
With palladium diacetate; 1,8-diazabicyclo[5.4.0]undec-7-ene; catacxium A In dimethyl sulfoxide at 120℃; for 24h;	85%

potassium 2-(pyridin-2-yl)acetate (106966-98-7) + 4-bromo-3-fluorotoluene (452-74-4) → 2-(2-fluoro-4-methylbenzyl)pyridine (1251919-74-0)

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In diethylene glycol dimethyl ether at 150℃; for 24h; Inert atmosphere;	82%

carbon monoxide (201230-82-2) + 4-bromo-3-fluorotoluene (452-74-4) + 3-amino-4-hydroxytoluene (95-84-1) → 3,8-dimethyldibenzo[b,f][1,4]oxazepin-11(10H)-one

Conditions	Yield
With palladium diacetate; 1,8-diazabicyclo[5.4.0]undec-7-ene; catacxium A In dimethyl sulfoxide at 120℃; for 24h;	81%

3-Sulfolene (77-79-2) + 4-bromo-3-fluorotoluene (452-74-4) → C11H11F

Conditions	Yield
With dichloro bis(acetonitrile) palladium(II); potassium tert-butylate; potassium hydrogencarbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In tetrahydrofuran at 110℃; diastereoselective reaction;	81%

carbon monoxide (201230-82-2) + 4-bromo-3-fluorotoluene (452-74-4) + 2-hydroxy-5-chloro-aniline (95-85-2) → 8-chloro-3-methyldibenzo[b,f][1,4]oxazepin-11(10H)-one

Conditions	Yield
With palladium diacetate; 1,8-diazabicyclo[5.4.0]undec-7-ene; catacxium A In dimethyl sulfoxide at 120℃; for 24h;	80%

4-bromo-3-fluorotoluene (452-74-4) + pentan-3-one (96-22-0) → 3-(2-fluoro-4-methyl-phenyl)-pentan-3-ol (737800-46-3)

Conditions	Yield
Stage #1: 4-bromo-3-fluorotoluene With n-butyllithium In hexanes; diethyl ether at -78℃; for 2.17h; Stage #2: pentan-3-one In hexanes; diethyl ether at -78 - 20℃; for 12h;	77%

4-bromo-3-fluorotoluene (452-74-4) + 3,5-dimethylphenyl boronic acid (172975-69-8) → C15H15F (1453806-84-2)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In tetrahydrofuran; water at 70℃; for 24h; Inert atmosphere;	75%

2-aminopyridine (504-29-0) + carbon monoxide (201230-82-2) + 4-bromo-3-fluorotoluene (452-74-4) → 3-methyl-11H-pyrido[2,1-b]quinazoline-11-one (70354-44-8)

Conditions	Yield
With palladium diacetate; 1,8-diazabicyclo[5.4.0]undec-7-ene; catacxium A In N,N-dimethyl acetamide at 120℃; under 11251.1 Torr; for 16h; Inert atmosphere; Autoclave;	75%

4-bromo-3-fluorotoluene (452-74-4) + 2-chloro-4-methyl-benzaldehyde (50817-80-6) → 2-chloro-2’-fluoro-4,4’-dimethylbenzhydrol

Conditions	Yield
Stage #1: 4-bromo-3-fluorotoluene With n-butyllithium In diethyl ether; hexane at -78℃; for 0.166667h; Stage #2: 2-chloro-4-methyl-benzaldehyde In diethyl ether; hexan-1-ol at -78℃; for 0.333333h;	75%

carbon monoxide (201230-82-2) + 4-bromo-3-fluorotoluene (452-74-4) + 2-amino-phenol (95-55-6) → 3-methyldibenzo[b,f][1,4]oxazepin-11(10H)-one (3158-86-9)

Conditions	Yield
With palladium diacetate; 1,8-diazabicyclo[5.4.0]undec-7-ene; catacxium A In dimethyl sulfoxide at 120℃; for 24h;	74%

phenyl benzyl ketone (451-40-1) + carbon monoxide (201230-82-2) + 4-bromo-3-fluorotoluene (452-74-4) → 7-methyl-2,3-diphenyl-4H-chromen-4-one

Conditions	Yield
With 1,3-bis-(diphenylphosphino)propane; palladium diacetate; caesium carbonate In N,N-dimethyl acetamide at 120℃; under 7500.75 Torr; for 20h; Autoclave;	74%

2-fluoro-4-methylphenylboronic acid (170981-26-7) + 4-bromo-3-fluorotoluene (452-74-4) → 2,2'-difluoro-4,4'-dimethyl-1,1'-biphenyl (388-83-0)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In methanol; water; toluene for 15h; Inert atmosphere; Reflux;	73%

2-amino-3-methylphenol (2835-97-4) + carbon monoxide (201230-82-2) + 4-bromo-3-fluorotoluene (452-74-4) → 3,9-dimethyldibenzo[b,f][1,4]oxazepin-11(10H)-one

Conditions	Yield
With palladium diacetate; 1,8-diazabicyclo[5.4.0]undec-7-ene; catacxium A In dimethyl sulfoxide at 120℃; for 24h;	72%

4-bromo-3-fluorotoluene (452-74-4) + copper(l) cyanide → 2-fluoro-4-methylbenzonitrile (85070-67-3)

Conditions	Yield
In N,N-dimethyl-formamide	70%
In DMF (N,N-dimethyl-formamide) for 12h; Heating / reflux;

4-bromo-3-fluorotoluene (452-74-4) + sodium methylate (124-41-4) → 1-bromo-2-methoxy-4-methylbenzene (95740-49-1)

Conditions	Yield
In dimethyl sulfoxide for 16h; Inert atmosphere; Reflux; Schlenk technique;	70%
In dimethyl sulfoxide at 130℃; for 12h;	65.8%

Upstream product

• 352-70-5 m-Fluorotoluene 
• 452-63-1 2-Bromo-5-fluorotoluene 
• 93765-84-5 2,4-dibromo-5-fluorotoluene 
• 75-16-1 methylmagnesium bromide 
• 136434-77-0 4-bromo-3-fluoroiodobenzene 
• 89-62-3 4-methyl-2-nitroaniline 
• 612-45-3 4-methyl-2-nitroacetanilide 
• 5326-34-1 4-Bromo-3-nitrotoluene 
• 53078-85-6 2-bromo-5-methylaniline 
• 56-23-5 tetrachloromethane 
• 7726-95-6 bromine 

Downstream Products

• 153556-42-4 4-bromo-3-fluorobenzoic acid 
• 127865-70-7 2-fluoro-4-methoxymethylbenzyl alcohol 
• 477199-77-2 4-(bromomethyl)-2-fluorobenzoic acid 
• 477199-78-3 2-fluoro-4-methoxymethylbenzoic acid 
• 127425-73-4 1-bromo-4-(bromomethyl)-2-fluorobenzene 
• 350587-20-1 1-bromo-4-(dibromomethyl)-2-fluorobenzene 
• 737800-46-3 3-(2-fluoro-4-methyl-phenyl)-pentan-3-ol 
• 85070-67-3 2-fluoro-4-methylbenzonitrile 
• 1403396-32-6 1-(4-bromo-3-fluorophenyl)cyclopropanecarbohydrazide 
• 1403395-30-1 {3-[1-(2-fluorobiphenyl-4-yl)cyclopropyl]-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-8-yl}methanol 
• 1403396-35-9 8-({[tert-butyl(dimethyl)silyl]oxy}methyl)-3-[1-(3-fluoro-4-pyridin-3-ylphenyl)cyclopropyl]-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepine 
• 1403395-31-2 {3-[1-(3-fluoro-4-pyridin-3-ylphenyl)cyclopropyl]-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-8-yl}methanol 
• 1403396-91-7 8-({[tert-butyl(dimethyl)silyl]oxy}methyl)-3-{1-[3-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl]cyclopropyl}-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepine 
• 1403395-87-8 (3-{1-[3-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl]cyclopropyl}-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-8-yl)methanol 

Relevant articles and documents

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