224185-19-7

Basic information

• Product Name: 4-Bromo-5-fluoro-2-nitrotoluene
• Synonyms: 4-BROMO-3-FLUORO-6-NITROTOLUENE;4-BROMO-5-FLUORO-2-NITROTOLUENE;4-Bromo-5-fluoro-2-nitortoluene;2-Nitro-4-Bromo-5-Fluorotoluene;1-Bromo-2-fluoro-4-methyl-5-nitro-benzene;Benzene,1-broMo-2-fluoro-4-Methyl-5-nitro-
• CAS NO: 224185-19-7
• Molecular Formula: C₇H₅BrFNO₂
• Molecular Weight: 234.02
• EINECS: 1533716-785-6
• Product Categories: Aromatic Hydrocarbons (substituted) & Derivatives;Halogen toluene;Miscellaneous;Nitro Compounds;Nitrogen Compounds;Organic Building Blocks
• Mol File: 224185-19-7.mol
• Article Data: 10

Chemical Properties

• Melting Point: 59-63°C
• Boiling Point: 266.6 °C at 760 mmHg
• Flash Point: 115.1 °C
• Appearance: /
• Density: 1.696 g/cm³
• Vapor Pressure: 0.0141mmHg at 25°C
• Refractive Index: 1.57
• Storage Temp.: Sealed in dry,Room Temperature
• CAS DataBase Reference: 4-Bromo-5-fluoro-2-nitrotoluene(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Bromo-5-fluoro-2-nitrotoluene(224185-19-7)
• EPA Substance Registry System: 4-Bromo-5-fluoro-2-nitrotoluene(224185-19-7)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 22-36-36/37/38
• Safety Statements: 26-36/37-36
• WGK Germany: 3
• Hazardous Substances Data: 224185-19-7(Hazardous Substances Data)

Usage

Chemical Properties

pale yellow powder

InChI:InChI=1/C7H5BrFNO2/c1-4-2-6(9)5(8)3-7(4)10(11)12/h2-3H,1H3

Synthetic route

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%

2-fluoro-4-methyl-5-nitro-phenylamine (259860-00-9) → 3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7)

Conditions	Yield
Stage #1: 2-fluoro-4-methyl-5-nitro-phenylamine With hydrogen bromide; sodium nitrite In water at 0 - 5℃; for 0.25h; Stage #2: With copper(I) oxide; hydrogen bromide In water at 0℃;	91%

3-fluoro-6-nitrotoluene (446-33-3) → 3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7)

Conditions	Yield
With sulfuric acid; bromine; silver nitrate In (2S)-N-methyl-1-phenylpropan-2-amine hydrate	83%

copper(I) bromide (7787-70-4) + 2-fluoro-4-methyl-5-nitro-phenylamine (259860-00-9) → 3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7)

Conditions	Yield
With sodium nitrite In water; hydrogen bromide	50%

sodium ethanolate (141-52-6) + 3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7) → 1-bromo-2-ethoxy-4-methyl-5-nitrobenzene (1226903-38-3)

Conditions	Yield
With sodium ethanolate In ethanol at 20℃; for 1h;	99%

1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyridin-2-one (1002309-52-5) + 3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7) → 5-(2-fluoro-4-methyl-5-nitrophenyl)-1-methylpyridin-2(1H)-one

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In 1,2-dimethoxyethane; water at 120℃; for 0.5h; Suzuki Coupling; Inert atmosphere; Microwave irradiation;	99%
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In 1,2-dimethoxyethane; water at 120℃; for 0.5h; Inert atmosphere; Microwave irradiation;	99%

2,4-difluorophenol (367-27-1) + 3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7) → 1-bromo-2-(2,4-difluorophenoxy)-4-methyl-5-nitrobenzene

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 20℃;	99%
With caesium carbonate In dimethyl sulfoxide at 100℃; for 3h;	3.8 g

3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7) → 5-bromo-4-fluoro-2-methylaniline (627871-16-3)

Conditions	Yield
With 2,3-dimethyl-2,3-butane diol; [MoO2Cl2(dmf)2] In o-xylene at 130℃; for 3h; chemoselective reaction;	95%
With iron; ammonium chloride In water for 48.5h; Heating / reflux;	72%
With ammonium chloride; iron In water for 48h; Heating / reflux;	72%

bis(pinacol)diborane (73183-34-3) + 3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7) → 2-(2-fluoro-4-methyl-5-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1510828-68-8)

Conditions	Yield
With [1,1'-bis(diphenylphosphino)-ferrocene]palladium(II) chloride-dichlormethane complex; potassium acetate In 1,4-dioxane at 100℃; for 1h; Suzuki Coupling; Inert atmosphere; Sealed tube;	91%
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate In 1,4-dioxane at 90℃; for 15h; Inert atmosphere;

methanol (67-56-1) + 3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7) → 1-bromo-2-methoxy-4-methyl-5-nitrobenzene (861076-28-0)

Conditions	Yield
Stage #1: methanol With sodium at 0℃; for 0.5h; Stage #2: 3-bromo-4-fluoro-6-methylnitrobenzene at 30℃; for 2h;	87.8%
With sodium at 40℃; for 2h; Cooling with ice;

3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7) → N-(5-bromo-4-fluoro-2-methylphenyl)iminodiacetic acid diethyl ester (1190892-54-6)

Conditions	Yield
	85%

N,N-dimethyl-formamide dimethyl acetal (4637-24-5) + 3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7) → [2-(4-bromo-5-fluoro-2-nitro-phenyl)-vinyl]-dimethyl-amine (1034894-73-9)

Conditions	Yield
In N,N-dimethyl-formamide at 125℃; for 3h;	83%

morpholine (110-91-8) + 3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7) → 4-(2-bromo-5-methyl-4-nitrophenyl)morpholine (1192471-65-0)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide for 3h;	77%
With potassium carbonate In N,N-dimethyl-formamide at 25℃; for 0.5h;	5.7 g

2-amino-phenol (95-55-6) + 3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7) → 3-methyl-2-nitro-10H-phenoxazine

Conditions	Yield
In dimethyl sulfoxide at 120℃; for 24h;	62%

2-Hydroxy-4-methylanilin (2835-98-5) + 3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7) → C14H12N2O3

Conditions	Yield
In dimethyl sulfoxide at 120℃; for 24h;	60%

3-amino-4-hydroxytoluene (95-84-1) + 3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7) → C14H12N2O3

Conditions	Yield
In dimethyl sulfoxide at 120℃; for 24h;	57%

2-hydroxy-5-chloro-aniline (95-85-2) + 3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7) → C13H9ClN2O3

Conditions	Yield
In dimethyl sulfoxide at 120℃; for 24h;	52%

3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7) → C7H4Br2FNO2

Conditions	Yield
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) In tetrachloromethane for 16h; Reflux;	50%

o-(N-methylamino)phenol (611-24-5) + 3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7) → C14H12N2O3

Conditions	Yield
In dimethyl sulfoxide at 120℃; for 24h;	48%

tert-butyl 2-((2S,6R)-4-(2-hydroxyethyl)-2,6-dimethylpiperazin-1-yl)acetate + 3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7) → tert-butyl 2-((2S,6R)-4-(2-(2-bromo-5-methyl-4-nitrophenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)acetate

Conditions	Yield
Stage #1: tert-butyl 2-((2S,6R)-4-(2-hydroxyethyl)-2,6-dimethylpiperazin-1-yl)acetate With sodium t-butanolate In tetrahydrofuran at 0℃; for 1h; Stage #2: 3-bromo-4-fluoro-6-methylnitrobenzene In tetrahydrofuran at 15℃; for 1h; Temperature;	44.4%

cyclohexanol (108-93-0) + 3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7) → 1-bromo-2-(cyclohexyloxy)-4-methyl-5-nitrobenzene (1351812-80-0)

Conditions	Yield
With potassium hydroxide In acetonitrile at 0 - 20℃; for 22h; Suzuki Coupling;	36%

aluminum nickel + N,N-dimethyl-formamide dimethyl acetal (4637-24-5) + 3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7) → 6-bromo-5-fluoro-1H-indole (259860-08-7)

Conditions	Yield
With hydrazine hydrate In tetrahydrofuran; methanol; N,N-dimethyl-formamide	16%

3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7) → 5-bromo-4-fluoro-2-methylbenzenethiol (873922-26-0)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 63 percent / SnCl2 / ethyl acetate 2.1: NaNO2; aq. HCl 2.2: potassium ethyl xanthogenate 2.3: 92 percent / KOH / ethanol View Scheme

3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7) → 4-bromo-5-fluoro-7-methyl-benzo[b]thiophen-3-one (873922-28-2)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: 63 percent / SnCl2 / ethyl acetate 2.1: NaNO2; aq. HCl 2.2: potassium ethyl xanthogenate 2.3: 92 percent / KOH / ethanol 3.1: pyridine / 0 °C 4.1: TFA / CH2Cl2 5.1: SOCl2 / 90 °C 6.1: AlCl3 / chlorobenzene View Scheme

3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7) → (5-bromo-4-fluoro-2-methyl-phenylsulfanyl)-acetyl chloride

Conditions	Yield
Multi-step reaction with 5 steps 1.1: 63 percent / SnCl2 / ethyl acetate 2.1: NaNO2; aq. HCl 2.2: potassium ethyl xanthogenate 2.3: 92 percent / KOH / ethanol 3.1: pyridine / 0 °C 4.1: TFA / CH2Cl2 5.1: SOCl2 / 90 °C View Scheme

3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7) → (5-bromo-4-fluoro-2-methyl-phenylsulfanyl)-acetic acid (873922-27-1)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: 63 percent / SnCl2 / ethyl acetate 2.1: NaNO2; aq. HCl 2.2: potassium ethyl xanthogenate 2.3: 92 percent / KOH / ethanol 3.1: pyridine / 0 °C 4.1: TFA / CH2Cl2 View Scheme

3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7) → 2-(4-bromo-5-fluoro-7-methyl-benzo[b]thiophen-3-yl)-ethanol (845746-23-8)

Conditions	Yield
Multi-step reaction with 8 steps 1.1: 63 percent / SnCl2 / ethyl acetate 2.1: NaNO2; aq. HCl 2.2: potassium ethyl xanthogenate 2.3: 92 percent / KOH / ethanol 3.1: pyridine / 0 °C 4.1: TFA / CH2Cl2 5.1: SOCl2 / 90 °C 6.1: AlCl3 / chlorobenzene 7.1: 39 percent / toluene / 120 °C 8.1: 83 percent / LiAlH4 / tetrahydrofuran / 0 °C View Scheme

3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7) → (5-bromo-4-fluoro-2-methyl-phenylsulfanyl)-acetic acid tert-butyl ester

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 63 percent / SnCl2 / ethyl acetate 2.1: NaNO2; aq. HCl 2.2: potassium ethyl xanthogenate 2.3: 92 percent / KOH / ethanol 3.1: pyridine / 0 °C View Scheme

3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7) → (4-bromo-5-fluoro-7-methyl-benzo[b]thiophen-3-yl)-acetic acid ethyl ester (873922-29-3)

Conditions	Yield
Multi-step reaction with 7 steps 1.1: 63 percent / SnCl2 / ethyl acetate 2.1: NaNO2; aq. HCl 2.2: potassium ethyl xanthogenate 2.3: 92 percent / KOH / ethanol 3.1: pyridine / 0 °C 4.1: TFA / CH2Cl2 5.1: SOCl2 / 90 °C 6.1: AlCl3 / chlorobenzene 7.1: 39 percent / toluene / 120 °C View Scheme

3-bromo-4-fluoro-6-methylnitrobenzene (224185-19-7) → (5-cyano-6-fluoro-8-methyl-1-propyl-3,4-dihydro-1H-[1]benzothieno[2,3-c]pyran-1-yl)acetic acid (845746-06-7)

Conditions

Yield

Multi-step reaction with 11 steps 1.1: 63 percent / SnCl2 / ethyl acetate 2.1: NaNO2; aq. HCl 2.2: potassium ethyl xanthogenate 2.3: 92 percent / KOH / ethanol 3.1: pyridine / 0 °C 4.1: TFA / CH2Cl2 5.1: SOCl2 / 90 °C 6.1: AlCl3 / chlorobenzene 7.1: 39 percent / toluene / 120 °C 8.1: 83 percent / LiAlH4 / tetrahydrofuran / 0 °C 9.1: 75 percent / BF3-Et2O / CH2Cl2 10.1: NMP / 0.25 h / 220 °C / microwave irradiation 11.1: aq. NaOH / ethanol; tetrahydrofuran View Scheme

Upstream product

• 7787-70-4 copper(I) bromide 
• 259860-00-9 2-fluoro-4-methyl-5-nitro-phenylamine 
• 446-33-3 5-Fluoro-2-nitrotoluene 
• 452-74-4 4-bromo-3-fluorotoluene 

Downstream Products

• 1034894-73-9 [2-(4-bromo-5-fluoro-2-nitro-phenyl)-vinyl]-dimethyl-amine 
• 861076-28-0 1-bromo-2-methoxy-4-methyl-5-nitrobenzene 

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