1996-29-8

Basic information

• Product Name: 1-Bromo-4-chloro-2-fluorobenzene
• Synonyms: 2-BROMO-5-CHLORO-1-FLUOROBENZENE;2-BROMO-5-CHLOROFLUOROBENZENE;2-FLUORO-4-CHLOROBROMOBENZENE;1-BROMO-4-CHLORO-2-FLUOROBENZENE;1-Bromo-4-chloro-2-fluorobenzene 97%;4-CHLORO-2-FLUORO BROMOBENZENE;1-Bromo-4-chloro-2-fluorobenzene97%;2-tert-Butyl-4-(dicyanomethylene)-6-[2-(1,1,7,7-tetramethyljulolidin-9-yl)vinyl]-4H-pyran [This reagent can be used without further purification for display device research, etc.]
• CAS NO: 1996-29-8
• Molecular Formula: C₆H₃BrClF
• Molecular Weight: 209.44
• Product Categories: Aromatic Halides (substituted);Bromine Compounds;Chlorine Compounds;Fluorine Compounds;Aryl;C6;Halogenated Hydrocarbons;Aromatics;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;Fluorine series
• Mol File: 1996-29-8.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 91-92 °C20 mm Hg(lit.)
• Flash Point: 198 °F
• Appearance: Clear colorless to pale yellow/Liquid
• Density: 1.678 g/mL at 25 °C(lit.)
• Refractive Index: n20/D 1.556(lit.)
• Storage Temp.: Sealed in dry,Room Temperature
• Water Solubility: INSOLUBLE
• BRN: 2081083
• CAS DataBase Reference: 1-Bromo-4-chloro-2-fluorobenzene(CAS DataBase Reference)
• NIST Chemistry Reference: 1-Bromo-4-chloro-2-fluorobenzene(1996-29-8)
• EPA Substance Registry System: 1-Bromo-4-chloro-2-fluorobenzene(1996-29-8)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 37/39-26-24/25
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 1996-29-8(Hazardous Substances Data)

Usage

Description

1-Bromo-4-chloro-2-fluorobenzene is a polyhalo substituted benzene derivative characterized by its clear colorless to pale yellow liquid appearance. It is known for its chemical reactivity, particularly in Suzuki coupling reactions with 2-cyanoarylboronic esters to form biphenyls, which are precursors for synthesizing 6-substituted phenanthridines. 1-Bromo-4-chloro-2-fluorobenzene also exhibits unique physical properties, such as an enthalpy of vaporization of 40.737 kJ/mol at its boiling point (467.15K).

Uses

Used in Pharmaceutical Industry:
1-Bromo-4-chloro-2-fluorobenzene is used as a starting material for the multi-step synthesis of AZD3264, an IKK2 (inhibitor of nuclear factor κ-B kinase-2) inhibitor. This application is significant due to its role in the development of potential treatments for various diseases and conditions that involve the IKK2 pathway.
Used in Chemical Synthesis:
In the field of chemical synthesis, 1-Bromo-4-chloro-2-fluorobenzene is utilized in the preparation of benzonorbornadiene derivatives. These derivatives are valuable intermediates in the synthesis of various complex organic compounds and have potential applications in material science and pharmaceuticals.
Used in Antimicrobial Applications:
1-Bromo-4-chloro-2-fluorobenzene is also recognized for its antibacterial and antifungal activities, making it a valuable compound in the development of new antimicrobial agents. This application is particularly important in the context of increasing antibiotic resistance and the need for novel, effective treatments against a wide range of microbial pathogens.

InChI:InChI=1/C6H3BrClF/c7-5-2-1-4(8)3-6(5)9/h1-3H

Synthetic route

2-bromo-5-chloroaniline hydrochloride → 1-bromo-4-chloro-2-fluorobenzene (1996-29-8)

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

2-fluoro-4-chloroaniline (57946-56-2) → 1-bromo-4-chloro-2-fluorobenzene (1996-29-8)

Conditions	Yield
Stage #1: 2-fluoro-4-chloroaniline With hydrogen bromide; sodium nitrite In water at -10℃; for 0.5h; Stage #2: With hydrogen bromide; copper(I) bromide In water at -10 - 55℃; for 0.333333h;

copper(I) sulfate + 2-fluoro-4-chloroaniline (57946-56-2) → 1-bromo-4-chloro-2-fluorobenzene (1996-29-8)

Conditions	Yield
With sodium bromide; copper(I) bromide; sodium sulfite; sodium nitrite In hydrogen bromide

1-bromo-4-chloro-2-fluorobenzene (1996-29-8) + 9H-carbazole (86-74-8) → 9-(2-bromo-5-chlorophenyl)-9H-carbazole

Conditions	Yield
With 18-crown-6 ether In dimethyl sulfoxide for 1h; Reflux;	99%
With sodium t-butanolate In N,N-dimethyl acetamide for 18h; Inert atmosphere; Heating;	90%
With 18-crown-6 ether; potassium fluoride on basic alumina In dimethyl sulfoxide for 8h; Inert atmosphere; Reflux;	83%

Ethyl isothiocyanate (542-85-8) + 1-bromo-4-chloro-2-fluorobenzene (1996-29-8) → 4-chloro-N-ethyl-2-fluorobenzenecarbothioamide (1269242-19-4)

Conditions	Yield
Stage #1: 1-bromo-4-chloro-2-fluorobenzene With n-butyllithium In tetrahydrofuran at -78℃; Stage #2: Ethyl isothiocyanate In diethyl ether at -78℃;	97%

carbon monoxide (201230-82-2) + 1-bromo-4-chloro-2-fluorobenzene (1996-29-8) + benzamidine monohydrochloride (1670-14-0) → 7-chloro-5-methyl-2-phenylquinazolin-4(3H)-one (7012-94-4)

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;	97%

tert-Butyl N-hydroxycarbamate (36016-38-3) + 1-bromo-4-chloro-2-fluorobenzene (1996-29-8) → t-butyl N-(5-bromo-2-chlorophenoxy) carbamate (1160491-84-8)

Conditions	Yield
With potassium hydroxide In dimethyl sulfoxide at 60℃; for 2h;	96%

1-bromo-4-chloro-2-fluorobenzene (1996-29-8) → (2-bromo-5-chlorophenyl)hydrazine (922552-53-2)

Conditions	Yield
With hydrazine hydrate In dimethyl sulfoxide at 70℃; for 72h;	96%

benzoimidazole (51-17-2) + 1-bromo-4-chloro-2-fluorobenzene (1996-29-8) → 1-(2-bromo-5-chlorophenyl)benzimidazole

Conditions	Yield
With potassium phosphate In N,N-dimethyl-formamide at 150℃;	93%

1-bromo-4-chloro-2-fluorobenzene (1996-29-8) + Benzyl isothiocyanate (622-78-6) → 4-chloro-2-fluoro-N-(phenylmethyl)benzenecarbothioamide (1269242-21-8)

Conditions	Yield
Stage #1: 1-bromo-4-chloro-2-fluorobenzene With n-butyllithium In tetrahydrofuran at -78℃; Stage #2: Benzyl isothiocyanate In diethyl ether at -78℃;	92%

1-bromo-4-chloro-2-fluorobenzene (1996-29-8) + (S)-3-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester (101469-92-5) → C15H19BrClNO3 (1609116-53-1)

Conditions	Yield
With potassium tert-butylate In 2-methyltetrahydrofuran Inert atmosphere;	90%

2-hydroxy-3-bromobenzaldehyde (1829-34-1) + 1-bromo-4-chloro-2-fluorobenzene (1996-29-8) → 2-bromo-6-[(4-chloro-2-fluorophenyl)(hydroxy)methyl]phenol

Conditions	Yield
Stage #1: 1-bromo-4-chloro-2-fluorobenzene With n-butyllithium In diethyl ether; hexane at -70 - -60℃; for 0.333333h; Stage #2: 2-hydroxy-3-bromobenzaldehyde In diethyl ether; hexane at -70 - -60℃; for 1h;	88%
Stage #1: 1-bromo-4-chloro-2-fluorobenzene With n-butyllithium In diethyl ether; hexane at -70 - 60℃; for 0.333333h; Stage #2: 2-hydroxy-3-bromobenzaldehyde In diethyl ether; hexane at -70 - -60℃; for 1h;	88%

1-bromo-4-chloro-2-fluorobenzene (1996-29-8) + (2,3-dimethoxyphenyl)boronic acid (40972-86-9) → C14H12ClFO2

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water for 21h; Inert atmosphere; Reflux;	88%

1-bromo-4-chloro-2-fluorobenzene (1996-29-8) + phenyl isothiocyanate (103-72-0) → 4-chloro-2-fluoro-N-phenylbenzenecarbothioamide (1269242-23-0)

Conditions	Yield
Stage #1: 1-bromo-4-chloro-2-fluorobenzene With n-butyllithium In tetrahydrofuran at -78℃; Stage #2: phenyl isothiocyanate In diethyl ether at -78℃;	86%

1-bromo-4-chloro-2-fluorobenzene (1996-29-8) + tert-butyl 2-methylpiperazine-1-carboxylate (120737-78-2) → C16H22ClFN2O2

Conditions	Yield
Stage #1: 1-bromo-4-chloro-2-fluorobenzene; tert-butyl 2-methylpiperazine-1-carboxylate With sodium t-butanolate In toluene at 80℃; Inert atmosphere; Stage #2: With tris(dibenzylideneacetone)dipalladium(0) chloroform complex; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In toluene for 18h; Reflux;	86%

1-bromo-4-chloro-2-fluorobenzene (1996-29-8) + 2-bromo-5-methoxy-benzaldehyde (7507-86-0) → (2-bromo-5-methoxyphenyl)(4-chloro-2-fluorophenyl)methanol (1449571-61-2)

Conditions	Yield
With n-butyllithium In diethyl ether; hexane at -78℃; for 0.166667h; Friedel-Crafts Acylation;	84%

3-Methylpyrazole (1453-58-3) + 1-bromo-4-chloro-2-fluorobenzene (1996-29-8) → 1-(2-bromo-5-chlorophenyl)-3-methyl-1H-pyrazole (1125828-26-3) + 1-(2-bromo-5-chlorophenyl)-5-methyl-1H-pyrazole (1125828-28-5)

Conditions	Yield
Stage #1: 3-Methylpyrazole With potassium tert-butylate In dimethyl sulfoxide at 20℃; for 0.25h; Stage #2: 1-bromo-4-chloro-2-fluorobenzene In dimethyl sulfoxide at 50℃; for 5h;	A 83% B 17%
Stage #1: 3-Methylpyrazole With potassium tert-butylate In dimethyl sulfoxide at 20℃; for 0.25h; Stage #2: 1-bromo-4-chloro-2-fluorobenzene In dimethyl sulfoxide at 50℃; for 5h;	A 83 %Chromat. B 17 %Chromat.
Stage #1: 3-Methylpyrazole With potassium tert-butylate In hexane; dimethyl sulfoxide at 50℃; for 0.5h; Stage #2: 1-bromo-4-chloro-2-fluorobenzene In hexane; dimethyl sulfoxide at 50℃; for 16h;
Stage #1: 3-Methylpyrazole With potassium tert-butylate In dimethyl sulfoxide at 50℃; for 0.5h; Stage #2: 1-bromo-4-chloro-2-fluorobenzene In dimethyl sulfoxide at 50℃; for 16h; Overall yield = 5.4 g;

1-bromo-4-chloro-2-fluorobenzene (1996-29-8) + 2-chloro-benzaldehyde (89-98-5) → (4-chloro-2-fluorophenyl)(2-chlorophenyl)methanol (1405713-80-5)

Conditions	Yield
With n-butyllithium In diethyl ether; hexane at -78℃; for 0.166667h; Friedel-Crafts Acylation;	83%

Trimethyl borate (121-43-7) + 1-bromo-4-chloro-2-fluorobenzene (1996-29-8) + water (7732-18-5) → 4-chloro-2-fluorophenylboronic acid (160591-91-3)

Conditions	Yield
Stage #1: 1-bromo-4-chloro-2-fluorobenzene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Stage #2: Trimethyl borate In tetrahydrofuran; hexane for 0.5h; Stage #3: water With hydrogenchloride In tetrahydrofuran; hexane at 20℃;	81%

carbon monoxide (201230-82-2) + 2-amino-4-fluorophenol (399-97-3) + 1-bromo-4-chloro-2-fluorobenzene (1996-29-8) → 3-chloro-8-fluorodibenzo[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%

carbon monoxide (201230-82-2) + 1-bromo-4-chloro-2-fluorobenzene (1996-29-8) + 2-Hydroxy-4-methylanilin (2835-98-5) → 3-chloro-7-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;	79%

1-bromo-4-chloro-2-fluorobenzene (1996-29-8) + 2-carbomethoxyaniline (134-20-3) → C14H11ClFNO2

Conditions	Yield
With bis(tri-tert-butylphosphine)palladium(0); caesium carbonate In toluene for 7h; Reflux;	77.1%

carbon monoxide (201230-82-2) + 1-bromo-4-chloro-2-fluorobenzene (1996-29-8) + 3-amino-4-hydroxytoluene (95-84-1) → 3-chloro-8-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;	77%

1-bromo-4-chloro-2-fluorobenzene (1996-29-8) → 3-bromo-6-chloro-2-fluorophenol (943830-14-6)

Conditions	Yield
Stage #1: 1-bromo-4-chloro-2-fluorobenzene With lithium diisopropyl amide In tetrahydrofuran; n-heptane; ethylbenzene at -78℃; for 0.5h; Stage #2: With Trimethyl borate In tetrahydrofuran; n-heptane; ethylbenzene at -78 - -20℃; for 1h; Stage #3: With peracetic acid In tetrahydrofuran; n-heptane; ethylbenzene at -78 - 20℃; for 12h;	76%
Stage #1: 1-bromo-4-chloro-2-fluorobenzene With lithium diisopropyl amide In tetrahydrofuran; n-heptane; ethylbenzene at -78 - -20℃; for 1h; Stage #2: With Trimethyl borate In tetrahydrofuran; n-heptane; ethylbenzene at -78 - 20℃; for 1h; Stage #3: With peracetic acid In tetrahydrofuran; n-heptane; ethylbenzene at -78℃; for 12h;	76%
Stage #1: 1-bromo-4-chloro-2-fluorobenzene With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78 - -20℃; Inert atmosphere; Stage #2: With Trimethyl borate In tetrahydrofuran; hexane at -78 - -20℃; Stage #3: With peracetic acid In tetrahydrofuran; hexane at -78 - 20℃; Inert atmosphere;	51%

carbon monoxide (201230-82-2) + 1-bromo-4-chloro-2-fluorobenzene (1996-29-8) + 2-amino-phenol (95-55-6) → 3-chlorodibenzo[b,f][1,4]oxazepin-11(10H)-one (3158-88-1)

Conditions	Yield
With palladium diacetate; 1,8-diazabicyclo[5.4.0]undec-7-ene; catacxium A In dimethyl sulfoxide at 120℃; for 24h;	75%

carbon monoxide (201230-82-2) + 1-bromo-4-chloro-2-fluorobenzene (1996-29-8) + 2-hydroxy-5-chloro-aniline (95-85-2) → 3,8-dichloro-dibenzo[b,f][1,4]oxazepin-11(10H)-one (908336-78-7)

Conditions	Yield
With palladium diacetate; 1,8-diazabicyclo[5.4.0]undec-7-ene; catacxium A In dimethyl sulfoxide at 120℃; for 24h;	75%

carbon monoxide (201230-82-2) + 1-bromo-4-chloro-2-fluorobenzene (1996-29-8) + 1,8-diazabicyclo[5.4.0]undec-7-ene (6674-22-2) → 11-chloro-1,2,3,4,6,7-hexahydro-4a,7a-diazacyclohepta[de]anthracen-8(5H)-one

Conditions	Yield
With palladium diacetate; catacxium A In N,N-dimethyl acetamide at 120℃; under 11251.1 Torr; for 21h; Inert atmosphere; Autoclave;	74%

1-bromo-4-chloro-2-fluorobenzene (1996-29-8) + (2,6-dimethoxyphenyl)boronic acid (23112-96-1) → C14H12ClFO2

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 80℃; for 12h; Inert atmosphere;	73%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 80℃; for 12h; Inert atmosphere;	73%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 60℃; for 12h;	51%

2-amino-3-methylphenol (2835-97-4) + carbon monoxide (201230-82-2) + 1-bromo-4-chloro-2-fluorobenzene (1996-29-8) → 3-chloro-9-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;	69%

2-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-5-(trifluoromethyl)benzonitrile (883898-98-4) + 1-bromo-4-chloro-2-fluorobenzene (1996-29-8) → 2-(4'-chloro-2'-fluorophenyl)-5-trifluoromethylbenzonitrile (883899-08-9)

Conditions	Yield
With potassium phosphate; palladium diacetate; triphenylphosphine In 1,4-dioxane at 80℃; for 16h; Suzuki coupling;	67%

Upstream product

• 57946-56-2 2-fluoro-4-chloroaniline 

Downstream Products

• 849766-57-0 4-(4-chloro-2-fluoro-benzyl)-piperidine 
• 1056987-23-5 C₁₇H₁₆BrClO₃ 
• 867367-03-1 [3-(2-bromo-5-chloro-phenoxy)-4-ethyl-phenyl]-acetic acid ethyl ester 

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