1435-48-9

Basic information

• Product Name: 1,3-Dichloro-4-fluorobenzene
• Synonyms: 2,4-Dichlorofluorobenzene 99%;2,4-Dichlorofluorobenzene99%;2,4-DICHLOROFLUOROBENZENECIPROFLOXACIN;DCFB 2,4-Dichlorofluorobenzen;1,3-Dichloro-4-fluorobenzene,99%;2,4-Dichloro-1-fluor;2,4- twochlorofluorobenzene;2,4-Dichlorofluobenzene
• CAS NO: 1435-48-9
• Molecular Formula: C₆H₃Cl₂F
• Molecular Weight: 164.99
• EINECS: 406-160-1
• Product Categories: Aromatic Hydrocarbons (substituted) & Derivatives;Fluorobenzene;Chlorine Compounds;Fluorine Compounds;Aryl;C6;Halogenated Hydrocarbons
• Mol File: 1435-48-9.mol
• Article Data: 10

Chemical Properties

• Melting Point: -23 °C
• Boiling Point: 172-174 °C(lit.)
• Flash Point: 98 °F
• Appearance: Clear colourless to yellow liquid
• Density: 1.409 g/mL at 25 °C(lit.)
• Vapor Pressure: 1.35mmHg at 25°C
• Refractive Index: n20/D 1.525(lit.)
• Storage Temp.: Flammables area
• Water Solubility: insoluble
• BRN: 2500791
• CAS DataBase Reference: 1,3-Dichloro-4-fluorobenzene(CAS DataBase Reference)
• NIST Chemistry Reference: 1,3-Dichloro-4-fluorobenzene(1435-48-9)
• EPA Substance Registry System: 1,3-Dichloro-4-fluorobenzene(1435-48-9)

Safety Data

• Hazard Codes: Xn,N,Xi
• Statements: 22-38-48/20/22-51/53-10-36/37/38
• Safety Statements: 36/37-61-16-36-26
• RIDADR: UN 1993 3/PG 3
• WGK Germany: 3
• HazardClass: 9
• PackingGroup: III
• Hazardous Substances Data: 1435-48-9(Hazardous Substances Data)

Usage

Chemical Properties

Clear colourless to yellow liquid

InChI:InChI=1/C6H3Cl2F/c7-4-1-2-6(9)5(8)3-4/h1-3H

Synthetic route

2,4-Dichloroaniline (554-00-7) → 1,3-dichloro-4-fluorobenzene (1435-48-9)

Conditions	Yield
Stage #1: 2,4-Dichloroaniline With hydrogenchloride; fluoroboric acid; sodium nitrite In water at 25℃; for 0.00555556h; Balz-Schiemann Reaction; Stage #2: In 1,2-dichloro-benzene at 190℃; for 0.0166667h; Balz-Schiemann Reaction;	93%
Stage #1: 2,4-Dichloroaniline With sodium tetrafluoroborate; sodium nitrite acidic conditions; Stage #2: at 150 - 170℃; Schieman reaction; Further stages.;

1,2,4-Trichlorobenzene (120-82-1) → 1,3-dichloro-4-fluorobenzene (1435-48-9)

Conditions	Yield
With potassium fluoride; 5,11,17,23,29,35-hexakis(tert-butyl)-37,38,39,40,41-hexakis(hydroxy)calix[6]arene In sulfolane at 185℃; for 5h; Reagent/catalyst; Temperature; Inert atmosphere; Sealed tube;	92%

3-chloro-4-fluoronitrobenzene (350-30-1) → 1,3-dichloro-4-fluorobenzene (1435-48-9)

Conditions	Yield
With chlorine at 170 - 180℃; for 8h; Temperature;	91.7%
Multi-step reaction with 2 steps 1: titanium (III)-chloride; water 2: aqueous HCl / Diazotization.Erwaermen der Diazoniumsalz-Loesung mit CuCl View Scheme

2,4-dichloroaniline hydrochloride (29084-76-2) → 1,3-dichloro-4-fluorobenzene (1435-48-9)

Conditions	Yield
Stage #1: 2,4-dichloroaniline hydrochloride With hydrogenchloride at -5℃; Stage #2: With tetrafluoroboric acid; sodium nitrite In water at 0℃; for 0.0833333h;	50.1%

3-chloro-4-fluorophenylamine (367-21-5) → 1,3-dichloro-4-fluorobenzene (1435-48-9)

Conditions	Yield
With hydrogenchloride Diazotization.Erwaermen der Diazoniumsalz-Loesung mit CuCl;

2,4-Dinitrofluorobenzene (70-34-8) → 1,3-dichloro-4-fluorobenzene (1435-48-9)

Conditions	Yield
With chlorine at 200℃;

2,3-dichlorofluorobenzene (36556-50-0) → 3,4-dichlorofluorobenzene (1435-49-0) + 3-chlorofluorobenzene (625-98-9) + 1,4-dichloro-2-fluorobenzene (348-59-4) + 1,3-dichloro-4-fluorobenzene (1435-48-9)

Conditions	Yield
In acetonitrile for 10h; Product distribution; Irradiation;	A 5 % Chromat. B 5 % Chromat. C 13 % Chromat. D 1 % Chromat.

2,4-dichlorophenylboronic acid (68716-47-2) → 1,3-dichloro-4-fluorobenzene (1435-48-9)

Conditions	Yield
With cesium fluoroxysulphate In methanol at -10℃; for 24h;	28 % Spectr.

(N-B)-Perhydro-2-(2,4-dichlorophenyl)-6-methyl-1,3-dioxa-6-aza-2-boracine → 1,3-dichloro-4-fluorobenzene (1435-48-9)

Conditions	Yield
With meta-dinitrobenzene; cesium fluoroxysulphate In acetonitrile Ambient temperature;	40 % Spectr.

fluorobenzene (462-06-6) + iron-powder → 3,4-dichlorofluorobenzene (1435-49-0) + 1-Chloro-4-fluorobenzene (352-33-0) + 1,3-dichloro-4-fluorobenzene (1435-48-9)

Conditions	Yield
Einleiten von 2 Mol Chlor;

2.4-dichloro-benzodiazonium-(1)-tetrafluoroborate → 1,3-dichloro-4-fluorobenzene (1435-48-9)

Conditions	Yield
Thermolysis;

4-Fluoronitrobenzene (350-46-9) → 1,3-dichloro-4-fluorobenzene (1435-48-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: iron-powder / Einleiten von Chlor 2: titanium (III)-chloride; water 3: aqueous HCl / Diazotization.Erwaermen der Diazoniumsalz-Loesung mit CuCl View Scheme

1,2-dichloro-benzene (95-50-1) → 1,3-dichloro-4-fluorobenzene (1435-48-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: nitric acid; sulfuric acid / 2 h / 95 - 100 °C 2.1: potassium fluoride / 3 h / 140 - 150 °C 2.2: 7 h / 165 - 170 °C 3.1: chlorine / 8 h / 170 - 180 °C View Scheme

3,4-dichloronitrobenzene (99-54-7) → 1,3-dichloro-4-fluorobenzene (1435-48-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: potassium fluoride / 3 h / 140 - 150 °C 1.2: 7 h / 165 - 170 °C 2.1: chlorine / 8 h / 170 - 180 °C View Scheme

C13H4Cl4F2O → 1,3-dichloro-4-fluorobenzene (1435-48-9) + C7H2Cl2FO2(1-)*Na(1+)

Conditions	Yield
Stage #1: C13H4Cl4F2O With sodium hydroxide at 90 - 100℃; for 1h; Stage #2: In 1,4-dioxane at 110 - 150℃; for 3h;

C13H4Cl4F2O → 1,3-dichloro-4-fluorobenzene (1435-48-9)

Conditions	Yield
With sodium hydroxide at 140 - 150℃; Temperature;

1,3-dichloro-4-fluorobenzene (1435-48-9) → 2,4-dichloro-5-fluoronitrobenzene (2105-59-1)

Conditions	Yield
With sulfuric acid; nitric acid at 50℃; for 2h; Temperature;	99.3%
With sulfuric acid; nitric acid at 50 - 60℃; for 3h;	98%
With sulfuric acid; potassium nitrate at 0 - 20℃; for 12h;	97%
With sulfuric acid; nitric acid
With sulfuric acid; sulfur trioxide; nitric acid

1,3-dichloro-4-fluorobenzene (1435-48-9) → 2,6-dichloro-3-fluorobenzenethiol

Conditions	Yield
Stage #1: 1,3-dichloro-4-fluorobenzene With n-butyllithium In tetrahydrofuran at -78℃; for 1.5h; Inert atmosphere; Stage #2: With sulfur In tetrahydrofuran at -78℃; for 2h; Inert atmosphere;	99%

carbon dioxide (124-38-9) + 1,3-dichloro-4-fluorobenzene (1435-48-9) → 2,4-dichloro-5-fluorobenzoyl chloride (86393-34-2)

Conditions	Yield
With Cationic resin catalyst In tetrachloromethane at 40 - 60℃; under 15001.5 Torr; for 5h; Pressure; Temperature; Reagent/catalyst;	98.8%

tetrachloromethane (56-23-5) + 1,3-dichloro-4-fluorobenzene (1435-48-9) → 1,5-dichloro-2-fluoro-4-(trichloromethyl)benzene

Conditions	Yield
With aluminum (III) chloride at 40℃; for 4h; Temperature;	95.2%
With phosphotungstic acid supported on magnetic ZrO2 for 0.5h; Autoclave; Reflux;	94%

1,3-dichloro-4-fluorobenzene (1435-48-9) + bis(pinacol)diborane (73183-34-3) → 2-(3,5-dichloro-2-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Conditions	Yield
With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; 4,4'-di-tert-butyl-2,2'-bipyridine In tetrahydrofuran at 80℃; for 6h; Inert atmosphere;	94%
With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; 4,4'-di-tert-butyl-2,2'-bipyridine In tetrahydrofuran at 80℃; for 18h; Inert atmosphere;
With (1,5-cyclooctadiene)(methoxy)iridium(l) dimer; 4,4'-di-tert-butyl-2,2'-bipyridine In tetrahydrofuran at 80℃; for 24h; Inert atmosphere;

methanol (67-56-1) + 1,3-dichloro-4-fluorobenzene (1435-48-9) → 1,3-dichloro-4-methoxybenzene (553-82-2)

Conditions	Yield
With 2,3-dicyano-5,6-dichloro-p-benzoquinone In 2,2,2-trifluoroethanol; 1,2-dichloro-ethane at 40℃; for 48h; Reagent/catalyst; Solvent; Irradiation;	94%

4-(3-((4-chloro-7-methoxyquinazolin-6-yl)oxy)propyl)morpholine (320366-66-3) + 1,3-dichloro-4-fluorobenzene (1435-48-9) → gefitinib (184475-35-2)

Conditions	Yield
With potassium carbonate; potassium iodide In N,N-dimethyl-formamide Reflux;	91%

1,3-dichloro-4-fluorobenzene (1435-48-9) + acetyl chloride (75-36-5) → 2,4-dichloro-5-fluoroacetophenone (704-10-9)

Conditions	Yield
With aluminum (III) chloride at 110℃; Reagent/catalyst; Temperature;	89.3%
With aluminum (III) chloride Friedel Crafts acylation;	52%
With aluminum (III) chloride at 30 - 120℃; Product distribution / selectivity;
aluminum (III) chloride

1,3-dichloro-4-fluorobenzene (1435-48-9) + isopropyl alcohol (67-63-0) → 2,4-dichloro-1-isopropoxybenzene (6851-40-7)

Conditions	Yield
With 2,3-dicyano-5,6-dichloro-p-benzoquinone In 2,2,2-trifluoroethanol; 1,2-dichloro-ethane at 40℃; for 48h; Irradiation;	89%

ethanol (64-17-5) + 1,3-dichloro-4-fluorobenzene (1435-48-9) → 2,4-dichloro-1-ethoxybenzene (5392-86-9)

Conditions	Yield
With 2,3-dicyano-5,6-dichloro-p-benzoquinone In 2,2,2-trifluoroethanol; 1,2-dichloro-ethane at 40℃; for 48h; Irradiation;	87%

Cyclopropylmethanol (2516-33-8) + 1,3-dichloro-4-fluorobenzene (1435-48-9) → 2,4-dichloro-1-(cyclopropylmethoxy)benzene

Conditions	Yield
With 2,3-dicyano-5,6-dichloro-p-benzoquinone In 2,2,2-trifluoroethanol; 1,2-dichloro-ethane at 40℃; for 48h; Irradiation;	87%

o-cyanobromobenzene (2042-37-7) + 1,3-dichloro-4-fluorobenzene (1435-48-9) → 5’-chloro-2’-fluoro-[1,1’-biphenyl]-2-carbonitrile

Conditions	Yield
With potassium pivalate; palladium dichloride In N,N-dimethyl acetamide at 150℃; for 16h; regioselective reaction;	86%

tetrachloromethane (56-23-5) + 1,3-dichloro-4-fluorobenzene (1435-48-9) → 2,4-dichloro-5-fluorobenzoyl chloride (86393-34-2)

Conditions	Yield
Stage #1: tetrachloromethane; 1,3-dichloro-4-fluorobenzene for 0.5h; Autoclave; Reflux; Stage #2: With water at 20 - 40℃; for 1h; Reagent/catalyst;	86%

Methyl formate (107-31-3) + 1,3-dichloro-4-fluorobenzene (1435-48-9) → 2,6-dichloro-3-fluorobenzaldehyde

Conditions	Yield
Stage #1: 1,3-dichloro-4-fluorobenzene With n-butyllithium In tetrahydrofuran at -78℃; for 1h; Inert atmosphere; Stage #2: Methyl formate In tetrahydrofuran at 10 - 15℃; for 16h; Inert atmosphere;	85.49%
Stage #1: 1,3-dichloro-4-fluorobenzene With n-butyllithium In tetrahydrofuran; hexanes at -78 - -70℃; for 2h; Inert atmosphere; Stage #2: Methyl formate In tetrahydrofuran; hexanes at -78℃; Inert atmosphere; Stage #3: With water; ammonium chloride In tetrahydrofuran; hexanes at 20℃; Inert atmosphere;
Stage #1: 1,3-dichloro-4-fluorobenzene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1.5h; Inert atmosphere; Stage #2: Methyl formate In tetrahydrofuran; hexane at -78 - 20℃; Inert atmosphere; Stage #3: With ammonium chloride In tetrahydrofuran; hexane; water

3,5-dimethoxyphenol (500-99-2) + 1,3-dichloro-4-fluorobenzene (1435-48-9) → 2,4-dichloro-1-(3,5-dimethoxyphenoxy)benzene (1379803-44-7)

Conditions	Yield
Stage #1: 3,5-dimethoxyphenol With caesium carbonate In 1-methyl-pyrrolidin-2-one at 50℃; for 0.5h; Inert atmosphere; Stage #2: 1,3-dichloro-4-fluorobenzene In 1-methyl-pyrrolidin-2-one at 120℃; for 2h; Inert atmosphere;	84%

1,3-dichloro-4-fluorobenzene (1435-48-9) + 1-(Trimethylsilyl)imidazole (18156-74-6) → trimethylsilyl fluoride (420-56-4) + 1-(2,4-dichlorophenyl)-1H-imidazole (190199-40-7)

Conditions	Yield
With cesium fluoride In N,N-dimethyl-formamide at 60℃; for 20h; Inert atmosphere;	A n/a B 80%

ethyl acetohydroximate (10576-12-2) + 1,3-dichloro-4-fluorobenzene (1435-48-9) → N-(2,4-Dichloro-phenoxy)-acetimidic acid ethyl ester

Conditions	Yield
With potassium tert-butylate In N,N-dimethyl-formamide 1.) r.t., 30 min, 2.) 80 deg C, 1.5 h;	77.8%

tetrachloromethane (56-23-5) + 1,3-dichloro-4-fluorobenzene (1435-48-9) → 1,5-dichloro-2-fluoro-4-(trichloromethyl)benzene + dichloro-bis(2,4-dichloro-5-fluorophenyl)methane

Conditions	Yield
at 40℃; for 2h; Temperature;	A 76.6% B 22.6%
With iron(III) chloride at 70℃; for 2h;	A 75.1% B 20.3%
With aluminum (III) chloride at 40℃; for 8h;	A 3.2 g B 13.5 g
With aluminum (III) chloride at 40℃; for 8h;

oxirane (75-21-8) + 1,3-dichloro-4-fluorobenzene (1435-48-9) → 2-(2,6-dichloro-3-fluorophenyl)ethanol

Conditions	Yield
Stage #1: 1,3-dichloro-4-fluorobenzene With n-butyllithium In tetrahydrofuran at -78℃; for 1h; Inert atmosphere; Stage #2: oxirane In tetrahydrofuran at -78℃; for 2h; Inert atmosphere;	75%
Stage #1: 1,3-dichloro-4-fluorobenzene With n-butyllithium In tetrahydrofuran at -78℃; for 1h; Stage #2: oxirane In tetrahydrofuran at -78℃; for 2h;	75%

3-bromoquinoline (5332-24-1) + 1,3-dichloro-4-fluorobenzene (1435-48-9) → 3-(3,5-dichloro-2-fluorophenyl)quinoline + C15H8Cl2FN + C15H8Cl2FN

Conditions	Yield
With potassium pivalate; palladium dichloride In N,N-dimethyl acetamide at 150℃; for 16h; regioselective reaction;	A 72% B n/a C n/a

(R)-4-(benzyl-methyl-amino)-1-tert-butoxy-butan-2-ol (865864-47-7) + 1,3-dichloro-4-fluorobenzene (1435-48-9) → (R)-benzyl-[4-tert-butoxy-3-(2,4-dichloro-phenoxy)-butyl]-methyl amine (865865-21-0)

Conditions	Yield
Stage #1: (R)-4-(benzyl-methyl-amino)-1-tert-butoxy-butan-2-ol With sodium hydride In dimethyl sulfoxide for 0.5h; Stage #2: 1,3-dichloro-4-fluorobenzene In dimethyl sulfoxide	71%

1,3-dichloro-4-fluorobenzene (1435-48-9) + 1-(Trimethylsilyl)imidazole (18156-74-6) → 1-(2,4-dichlorophenyl)-1H-imidazole (190199-40-7)

Conditions	Yield
With copper(l) iodide In methanol; N,N-dimethyl-formamide at 100℃; Inert atmosphere;	70%

1,3-dichloro-4-fluorobenzene (1435-48-9) → 2,4-dichloro-5-fluoro-benzoic acid (86522-89-6)

Conditions	Yield
	66%
Multi-step reaction with 3 steps 1: 2 h / 40 °C 2: iron(III) chloride; water / 90 °C 3: potassium perchlorate / N,N-dimethyl-formamide / Reflux View Scheme

4-bromobenzenecarbonitrile (623-00-7) + 1,3-dichloro-4-fluorobenzene (1435-48-9) → C13H6Cl2FN + C13H6Cl2FN + 3’,5’-dichloro-2’-fluoro-[1,1’-biphenyl]-4-carbonitrile

Conditions	Yield
With potassium pivalate; palladium dichloride In N,N-dimethyl acetamide at 150℃; for 16h; regioselective reaction;	A n/a B n/a C 66%

1,3-dichloro-4-fluorobenzene (1435-48-9) + 4-bromo-benzaldehyde (1122-91-4) → C13H7Cl2FO + C13H7Cl2FO + 3’,5’-dichloro-2’-fluoro-[1,1’-biphenyl]-4-carbaldehyde

Conditions	Yield
With potassium pivalate; palladium dichloride In N,N-dimethyl acetamide at 150℃; for 16h; regioselective reaction;	A n/a B n/a C 66%

1,3-dichloro-4-fluorobenzene (1435-48-9) + cyclohexanol (108-93-0) → 2,4-dichloro-1-(cyclohexyloxy)benzene

Conditions	Yield
With 2,3-dicyano-5,6-dichloro-p-benzoquinone In 2,2,2-trifluoroethanol; 1,2-dichloro-ethane at 40℃; for 48h; Irradiation;	64%

1,3-dichloro-4-fluorobenzene (1435-48-9) → C6H2Cl3FO2S

Conditions	Yield
With chlorosulfonic acid at 100℃; for 12h;	63%

Upstream product

• 462-06-6 fluorobenzene 
• 554-00-7 2,4-Dichloroaniline 
• 120-82-1 1,2,4-Trichlorobenzene 
• 29084-76-2 2,4-dichloroaniline hydrochloride 
• 99-54-7 3,4-dichloronitrobenzene 
• 95-50-1 1,2-dichloro-benzene 
• 350-46-9 4-Fluoronitrobenzene 
• 350-30-1 3-chloro-4-fluoronitrobenzene 
• 68716-47-2 2,4-dichlorophenylboronic acid 
• 36556-50-0 2,3-dichlorofluorobenzene 
• 70-34-8 2,4-Dinitrofluorobenzene 
• 367-21-5 3-chloro-4-fluorophenylamine 

Downstream Products

• 86393-34-2 2,4-dichloro-5-fluorobenzoyl chloride 
• 86522-89-6 2,4-dichloro-5-fluoro-benzoic acid 
• 1283142-17-5 (S)-2-(1-(4-(2,4-dichlorophenoxy)phenyl)pyrrolidin-2-yl)acetic acid trifluoroacetic acid salt 

Relevant articles and documents

Environment-friendly production process of 2, 4-dichloro-5-fluorobenzoyl chloride

The present invention relates to the field of chemistry, and particularly provides a preparation method of 2, 4-dichloro-5-fluorobenzoyl chloride. According to the invention, dimerization by-productsof the 2, 4-dichloro-5-fluorobenzoyl chloride produced by a carbon tetrachloride method are subjected to alkaline hydrolysis under the action of a catalyst, then after acidification, the processed product reacts with trichloride generated by condensation of a main reaction to be converted into 2, 4-dichloro-5-fluorobenzoyl chloride, and the yield reaches over 99.8%.

Preparation method for fluoroquinolones intermediate 2,4-dichloro-5-fluorobenzoyl chloride

The invention discloses a preparation method for fluoroquinolones intermediate 2,4-dichloro-5-fluorobenzoyl chloride, and belongs to the technical field of the pharmaceutical synthesis. Through changing a compound IV into a compound V* and raw material 2,4-dichlor fluorbenzene, easy explosive materials of hydrogen peroxide and the like are avoided from being used. The compound V*, through a one-step reaction, is changed into the compound 2,4-dichloro-5-fluorobenzoyl chloride. A synthesized product is higher in purity, a total yield of a two-step reaction is higher, the generated starting raw material 2,4-dichlor fluorbenzene can be recycled, and carboxylate (V*) is changed into acyl chloride (II), and hydrochloric acid is not generated, pollution can be reduced. The method is more superiorto an existing technology, capable of increasing a resource utilization rate, reducing a production risk, reducing production cost, and more suitable for industrial production.

O-dichlorobenzene with a quinolone drugs for coproduction method of key intermediate

The invention relates to the field of methods for preparing medicinal intermediates, in particular to the field of methods for preparing key intermediates of quinolone medicines, and develops a method for coproducing the key intermediates of the quinolone medicines by using o-dichlorobenzene as a raw material. The method comprises the following steps of: nitrifying the o-dichlorobenzene serving as the raw material, and performing distillation, purification and stepwise crystallization to obtain 2,3-dichloronitrobenzene and 3,4-dichloronitrobenzene; performing fluoridation on the 2,3-dichloronitrobenzene to obtain 3-chloro-2-fluoronitrobenzene, performing chlorination to obtain 2,6-dichlorofluorobenzene, performing nitration to obtain 1,3-dichloro-2-fluoro-4-nitrobenzene, and finally performing fluoridation to obtain 2,3,4-trifluoronitrobenzene; and performing fluoridation on the 2,3,4-trifluoronitrobenzene to obtain 3-chloro-4-fluoronitrobenzene, performing chlorination to obtain 1,3-dichloro-4-fluorobenzene, and finally performing acylation reaction on the 1,3-dichloro-4-fluorobenzene and acetylchloride to obtain 2,4-dichloro-5-fluoroacetophenone.