393-37-3

Basic information

• Product Name: 2-Fluoro-5-bromobenzotrifluoride
• Synonyms: 5-Bromo-alpha,alpha,alpha,2-tetrafluorotoluene 4-Bromo-1-fluoro-2-(trifluoromethyl)benzene;5--2-of fluorinebroMinethree fluorine toluene;2-FLUORO-5-BROMO BENZOTRIFLUORIDE;4-BROMO-1-FLUORO-2-(TRIFLUOROMETHYL)BENZENE;4-FLUORO-3-(TRIFLUOROMETHYL)BROMOBENZENE;5-BROMO-ALPHA,ALPHA,ALPHA,2-TETRAFLUOROTOLUENE;5-BROMO-2-FLUOROBENZOTRIFLUORIDE;2-Fluoro-5-BromotrifluoromethylBenzene
• CAS NO: 393-37-3
• Molecular Formula: C₇H₃BrF₄
• Molecular Weight: 243
• Product Categories: Building Blocks;Chemical Synthesis;Fluorinated Building Blocks;Halogenated Hydrocarbons;Organic Building Blocks;Organic Fluorinated Building Blocks;Other Fluorinated Organic Building Blocks;alkyl bromide| alkyl Fluorine;Trifluoromethylbenzene serise;Fluorobenzene;Miscellaneous;Benzotrifluoride Series;Aryl;C7;Halogenated Hydrocarbons;Aryl Fluorinated Building Blocks
• Mol File: 393-37-3.mol
• Article Data: 5

Chemical Properties

• Melting Point: 203 °C(Solv: hexane (110-54-3))
• Boiling Point: 79-80 °C50 mm Hg(lit.)
• Flash Point: >230 °F
• Appearance: Clear colorless to pale yellow/Liquid
• Density: 1.72 g/mL at 25 °C(lit.)
• Vapor Pressure: 2.77mmHg at 25°C
• Refractive Index: n20/D 1.462(lit.)
• Storage Temp.: Room temperature.
• Water Solubility: Soluble in water 700 g/L (20°C)
• BRN: 2643550
• CAS DataBase Reference: 2-Fluoro-5-bromobenzotrifluoride(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Fluoro-5-bromobenzotrifluoride(393-37-3)
• EPA Substance Registry System: 2-Fluoro-5-bromobenzotrifluoride(393-37-3)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 36/37/38-20/21/22
• Safety Statements: 23-24/25-36-26-37
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 393-37-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Intermediates:
2-Fluoro-5-bromobenzotrifluoride is used as a pharmaceutical intermediate for the synthesis of various medicinal compounds. Its unique structure allows for the creation of molecules with specific properties that can be tailored for therapeutic applications.
Used in the Preparation of Poly(arylene ether)s (PAEs):
In the chemical industry, 2-Fluoro-5-bromobenzotrifluoride is used as a key component in the preparation of poly(arylene ether)s (PAEs). These polymers are known for their excellent thermal stability, mechanical properties, and chemical resistance, making them suitable for a wide range of applications, including electronics, automotive, and aerospace industries.
Used in the Synthesis of Specific Compounds:
2-Fluoro-5-bromobenzotrifluoride is also utilized in the synthesis of specific compounds such as 3,5-bis(4-fluoro-3-trifluoromethylphenyl)phenol, 9,9-bis(2-ethylhexyl)-2,7-bis[4-fluoro-3-trifluoromethylphenyl]-9H-fluorene, and 3-trifluoromethyl-4-fluoro phenyl boronic acid. These compounds have potential applications in various fields, including materials science, electronics, and pharmaceuticals.

Synthesis Reference(s)

Journal of the American Chemical Society, 69, p. 2022, 1947 DOI: 10.1021/ja01200a060

InChI:InChI=1/C7H3BrF4/c8-4-1-2-6(9)5(3-4)7(10,11)12/h1-3H

Synthetic route

4-Fluoro-3-trifluoromethylaniline (2357-47-3) → 5-bromo-2-fluorobenzotrifluoride (393-37-3)

Conditions	Yield
With tert.-butylnitrite; copper(ll) bromide In acetonitrile at 20℃; Cooling with ice; Inert atmosphere;
With tert.-butylnitrite; copper(ll) bromide In acetonitrile at 20℃; for 2h; Inert atmosphere; Cooling with ice;
With tert.-butylnitrite; copper(ll) bromide In acetonitrile at 20℃; for 2h; Cooling with ice; Inert atmosphere;
With tert.-butylnitrite; copper(ll) bromide In acetonitrile at 20℃; for 2h; Inert atmosphere; Cooling with ice;	2 g

1-fluoro-2-trifluoromethylbenzene (392-85-8) → 5-bromo-2-fluorobenzotrifluoride (393-37-3)

Conditions	Yield
With ferric(III) bromide; sulfuric acid; tetrabutylammomium bromide; bromine; lithium bromide at 35 - 45℃; for 6h;	93.98%

5-bromo-1-trifluoromethyl-benzenediazonium-(2)-tetrafluoroborate → 5-bromo-2-fluorobenzotrifluoride (393-37-3)

5-bromo-2-fluorobenzotrifluoride (393-37-3) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → 5-bromo-2-fluoro-3-(trifluoromethyl)benzaldehyde (1291487-26-7)

Conditions	Yield
Stage #1: 5-bromo-2-fluorobenzotrifluoride With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1h; Inert atmosphere; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran at -78 - 20℃; Inert atmosphere;	72%
Stage #1: 5-bromo-2-fluorobenzotrifluoride With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1h; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran at -78℃; for 1h;	71.7%
Stage #1: 5-bromo-2-fluorobenzotrifluoride With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1h; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran at -78℃; for 1h;	71.7%
Stage #1: 5-bromo-2-fluorobenzotrifluoride With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1h; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran at -78℃; for 1h;	71.7%
Stage #1: 5-bromo-2-fluorobenzotrifluoride With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1h; Stage #2: N,N-dimethyl-formamide In N,N-dimethyl-formamide at -78℃; for 1h;	71.7%

pyrrolidin-3-ol (40499-83-0) + 5-bromo-2-fluorobenzotrifluoride (393-37-3) → 1-[4-fluoro-3-(trifluoromethyl)phenyl]pyrrolidin-3-ol (1198181-19-9)

Conditions	Yield
With caesium carbonate; palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In toluene at 90℃; for 16h; Inert atmosphere;	58%
With caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; palladium diacetate In toluene at 90℃; for 16h; Inert atmosphere;	58%

5-bromo-2-fluorobenzotrifluoride (393-37-3) + sodium thiomethoxide (5188-07-8) → (4-bromo-2-(trifluoromethyl)phenyl)(methyl)sulfane (300356-31-4)

Conditions	Yield
In water; N,N-dimethyl-formamide at 50℃; for 2h;	94%
In water; N,N-dimethyl-formamide at 50℃; for 2h;	94%
In N,N-dimethyl-formamide at 50℃; for 1h;
In N,N-dimethyl-formamide at 20 - 50℃;
In N,N-dimethyl-formamide at 50℃; for 1h;

5-bromo-2-fluorobenzotrifluoride (393-37-3) + 1-t-Butoxycarbonylpiperazine (57260-71-6) → 4-(4-fluoro-3-trifluoromethyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (1221069-81-3)

Conditions	Yield
With palladium diacetate; caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In toluene at 100℃; for 24h; Heating;	100%

ethyl trifluoroacetate, (383-63-1) + 5-bromo-2-fluorobenzotrifluoride (393-37-3) → 2,2,2-trifluoro-1-[4-fluoro-3-(trifluoromethyl)phenyl]ethanone (1335013-55-2)

Conditions	Yield
With n-butyllithium In tetrahydrofuran; hexane at -100 - -20℃;	86%

3-phenyl-2,2-bis(3-(trifluoromethoxy)phenyl)propan-1-amine (1032189-06-2) + 5-bromo-2-fluorobenzotrifluoride (393-37-3) → 4-fluoro-N-(3-phenyl-2,2-bis(3-(trifluoromethoxy)phenyl)propyl)-3-(trifluoromethyl)benzenamine (1032187-97-5)

Conditions	Yield
With 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate; tris-(dibenzylideneacetone)dipalladium(0) In toluene at 100℃;	32%

2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (61676-62-8) + 5-bromo-2-fluorobenzotrifluoride (393-37-3) → 2-(4-Fluoro-3-trifluoromethyl-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane

Conditions	Yield
Stage #1: 5-bromo-2-fluorobenzotrifluoride With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Inert atmosphere; Stage #2: 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane In tetrahydrofuran; hexane at 20℃; for 12h; Inert atmosphere;	82%

5-bromo-2-fluorobenzotrifluoride (393-37-3) + 3-hydroxy-benzeneacetic acid, methyl ester (42058-59-3) → methyl 2-[3-[4-bromo-2-(trifluoromethyl)phenoxy]phenyl]acetate

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 100℃;	55%

5-bromo-2-fluorobenzotrifluoride (393-37-3) + isopropyl alcohol (67-63-0) → 4-bromo-1-[(1-methylethyl)oxy]-2-(trifluoromethyl)benzene (914635-61-3)

Conditions	Yield
Stage #1: isopropyl alcohol With potassium tert-butylate In tetrahydrofuran at 50℃; for 0.166667h; Inert atmosphere; Stage #2: 5-bromo-2-fluorobenzotrifluoride In tetrahydrofuran at 50℃;
Stage #1: isopropyl alcohol With potassium tert-butylate In tetrahydrofuran at 50℃; for 0.166667h; Inert atmosphere; Stage #2: 5-bromo-2-fluorobenzotrifluoride In tetrahydrofuran at 50℃;
Stage #1: isopropyl alcohol With potassium tert-butylate In tetrahydrofuran at 50℃; for 0.166667h; Inert atmosphere; Stage #2: 5-bromo-2-fluorobenzotrifluoride In tetrahydrofuran at 50℃;
Stage #1: isopropyl alcohol With potassium tert-butylate In tetrahydrofuran at 50℃; for 0.166667h; Stage #2: 5-bromo-2-fluorobenzotrifluoride In tetrahydrofuran at 50℃;	5.21 g

5-bromo-2-fluorobenzotrifluoride (393-37-3) + 6-chloropyridin-3-ylboronic acid (444120-91-6) → C12H6ClF4N

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In tetrahydrofuran; water at 70℃; for 2h; Inert atmosphere; Reflux;	53%

octanol (111-87-5) + 5-bromo-2-fluorobenzotrifluoride (393-37-3) → 4-bromo-1-(octyloxy)-2-(trifluoromethyl)benzene (161712-25-0)

Conditions	Yield
With potassium tert-butylate In tetrahydrofuran Heating / reflux;	100%

t-butylsulfonamide (34813-49-5) + 5-bromo-2-fluorobenzotrifluoride (393-37-3) → N-(4-bromo-2-(trifluoromethyl)phenyl)-2-methylpropane-2-sulfonamide (1442431-99-3)

Conditions	Yield
Stage #1: t-butylsulfonamide With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.5h; Stage #2: 5-bromo-2-fluorobenzotrifluoride In N,N-dimethyl-formamide; mineral oil at 120℃;	31%

5-bromo-2-fluorobenzotrifluoride (393-37-3) + 4-pyridylboronic acid (1692-15-5) → 4-(4-fluoro-3-trifluoromethyl-phenyl)-pyridine (388118-59-0)

Conditions	Yield
With palladium diacetate; triphenylphosphine In propan-1-ol; water for 4h; Suzuki coupling; Heating;	82%
With sodium carbonate; triphenylphosphine; palladium diacetate In propan-1-ol; hexane; water

5-bromo-2-fluorobenzotrifluoride (393-37-3) + 2-(Dimethylaminophenylmethyl)cyclohexanone (94318-23-7) → 2-(dimethylaminophenylmethyl)-1-(4-fluoro-3-trifluoromethylphenyl)cyclohexanol, hydrochloride (300658-92-8)

Conditions	Yield
With magnesium In ethyl acetate	63.7%

5-bromo-2-fluorobenzotrifluoride (393-37-3) + (S)-2-amino-2,4-dimethylpentan-1-ol → (S)-1-(4-bromo-2-(trifluoromethyl)phenoxy)-2,4-dimethylpentan-2-amine

Conditions	Yield
Stage #1: (S)-2-amino-2,4-dimethylpentan-1-ol With potassium tert-butylate In tetrahydrofuran for 0.0833333h; Inert atmosphere; Stage #2: 5-bromo-2-fluorobenzotrifluoride In tetrahydrofuran at 20℃; for 2h; Inert atmosphere;
Stage #1: (S)-2-amino-2,4-dimethylpentan-1-ol With potassium tert-butylate In tetrahydrofuran for 0.0833333h; Inert atmosphere; Stage #2: 5-bromo-2-fluorobenzotrifluoride In tetrahydrofuran at 20℃; for 2h; Inert atmosphere;

2-(4-Fluorophenyl)ethanol (7589-27-7) + 5-bromo-2-fluorobenzotrifluoride (393-37-3) → 4-bromo-1-(4-fluorophenethoxy)-2-(trifluoromethyl)benzene

Conditions	Yield
With potassium tert-butylate In N,N-dimethyl-formamide for 2h;	62%

2-(phenyl)pyrrolidine (1006-64-0) + 5-bromo-2-fluorobenzotrifluoride (393-37-3) → 1-(4-bromo-2-(trifluoromethyl)phenyl)-2-phenylpyrrolidine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 150℃; Sealed tube;	4.9%

5-bromo-2-fluorobenzotrifluoride (393-37-3) + methyl(2-hydroxyethyl)carbamic acid tert-butyl ester (57561-39-4) → tert-butyl 2-(4-bromo-2-(trifluoromethyl)phenoxy)ethyl(methyl)carbamate (1315465-33-8)

Conditions	Yield
With sodium hydride; triethylamine In N,N-dimethyl-formamide at 20℃;

5-bromo-2-fluorobenzotrifluoride (393-37-3) + bis(pinacol)diborane (73183-34-3) → 2-(4-Fluoro-3-trifluoromethyl-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In 1,4-dioxane at 110℃; for 0.166667h; Miyaura Borylation Reaction; Microwave irradiation;

3-oxabicyclo[3.1.0]hexane-2,4-dione (5617-74-3) + 5-bromo-2-fluorobenzotrifluoride (393-37-3) → 2-[4-fluoro-3-(trifluoromethyl)benzoyl]cyclopropane-1-carboxylic acid

Conditions	Yield
Stage #1: 5-bromo-2-fluorobenzotrifluoride With iodine; magnesium In tetrahydrofuran at 40℃; Stage #2: 3-oxabicyclo[3.1.0]hexane-2,4-dione In tetrahydrofuran at -73℃; for 0.5h;

5-bromo-2-fluorobenzotrifluoride (393-37-3) + 4-tert-butyl-dimethylsilyloxyphenylboronic acid anhydride (123088-32-4) → 4'-fluoro-3'-trifluoromethyl-biphenyl-4-ol (634192-41-9)

Conditions	Yield
With sodium carbonate; tetrakis(triphenylphosphine) palladium(0) In 1,2-dimethoxyethane; water at 95℃; Suzuki reaction;	62%

5-bromo-2-fluorobenzotrifluoride (393-37-3) + bis(pinacol)diborane (73183-34-3) → C13H14BBrF4O2

Conditions	Yield
With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; 4,4'-di-tert-butyl-2,2'-bipyridine In tetrahydrofuran at 20℃; for 24h; Catalytic behavior; Inert atmosphere; Glovebox;	62%
With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; 4,4'-di-tert-butyl-2,2'-bipyridine In tetrahydrofuran at 20℃; for 24h; Inert atmosphere; Glovebox;	62%

5-bromo-2-fluorobenzotrifluoride (393-37-3) → 5-bromo-2-fluoro-1-nitro-3-trifluoromethyl-benzene (889459-12-5) + 1-bromo-4-fluoro-2-nitro-5-trifluoromethyl-benzene (889459-13-6)

Conditions	Yield
With sulfuric acid; nitric acid at 15 - 30℃; for 4h;

5-bromo-2-fluorobenzotrifluoride (393-37-3) + sodium thioethylate (811-51-8) → 4-bromo-1-(ethylthio)-2-(trifluoromethyl)-benzene (873194-97-9)

Conditions	Yield
In N,N-dimethyl-formamide at 50℃; for 1.5h;

5-bromo-2-fluorobenzotrifluoride (393-37-3) + potassium cyanide (151-50-8) → 4-bromo-2-(trifluoromethyl)benzonitrile (191165-13-6)

Conditions	Yield
In dimethyl sulfoxide at 80℃; for 14h;

Upstream product

• 2357-47-3 4-Fluoro-3-trifluoromethylaniline 
• 392-85-8 1-fluoro-2-trifluoromethylbenzene 

Downstream Products

• 634192-41-9 4'-fluoro-3'-trifluoromethyl-biphenyl-4-ol 
• 388118-59-0 4-(4-fluoro-3-trifluoromethyl-phenyl)-pyridine 
• 161712-25-0 4-bromo-1-(octyloxy)-2-(trifluoromethyl)benzene 
• 889459-12-5 5-bromo-2-fluoro-1-nitro-3-(trifluoromethyl)benzene 
• 889459-13-6 1-bromo-4-fluoro-2-nitro-5-trifluoromethyl-benzene 
• 873194-97-9 4-bromo-1-(ethylthio)-2-(trifluoromethyl)-benzene 
• 300356-31-4 (4-bromo-2-(trifluoromethyl)phenyl)(methyl)sulfane 
• 864878-67-1 1-(4-fluoro-3-trifluoromethyl-phenyl)-2-methyl-propan-1-ol 
• 1240928-55-5 C₉H₄ClF₅O 
• 1259293-45-2 C₃₉H₂₀F₈ 
• 1259293-44-1 C₃₆H₂₆F₈ 
• 1259293-46-3 C₃₉H₂₂F₈ 
• 1259293-47-4 C₃₉H₂₀F₈O 
• 182344-23-6 4-fluoro-3-(trifluoromethyl)phenylboronic acid 

Relevant articles and documents

A process for preparing 2 - bromo - 5 - fluoro-toluene method

The invention discloses a method for preparing 2-bromine-5-fluorobenzotrifluoride. According to the preparation method, fluorobenzotrifluoride serves as a raw material, under the condition of concentrated sulfuric acid and composite catalysts, bromine is stirred and added dropwise, and 2-bromine-5-fluorobenzotrifluoride is obtained after separation and purification. The yield reaches over 91.1%, the reaction conversion rate is larger than 99%, and selectivity is 92-95%. The raw material applied in the reaction process is convenient to purchase, production cost is low, waste acid obtained in the reaction process can be recycled, post-processing is easy, and the whole technology does not generate a large amount of wastewater containing salt and organic matter. Economic benefits and social benefits are good.

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