452-09-5

Basic information

• Product Name: 4-CHLORO-2-FLUOROANISOLE
• Synonyms: 4-CHLORO-2-FLUOROANISOLE;4-Chloro-2-fluoroanisole 98%;4-Chloro-2-fluoroanisole98%;2-Fluoro-4-chloroanisole;4-Chloro-2-fluoro-1-methoxybenzene
• CAS NO: 452-09-5
• Molecular Formula: C₇H₆ClFO
• Molecular Weight: 160.57
• Product Categories: Aromatic Ethers;Anisole;Anisoles, Alkyloxy Compounds & Phenylacetates;Chlorine Compounds;Fluorine Compounds;Ethers;Organic Building Blocks;Oxygen Compounds
• Mol File: 452-09-5.mol
• Article Data: 7

Chemical Properties

• Boiling Point: 160 °C(lit.)
• Flash Point: 175 °F
• Appearance: /
• Density: 1.294 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.8mmHg at 25°C
• Refractive Index: n20/D 1.518(lit.)
• Storage Temp.: Sealed in dry,Room Temperature
• CAS DataBase Reference: 4-CHLORO-2-FLUOROANISOLE(CAS DataBase Reference)
• NIST Chemistry Reference: 4-CHLORO-2-FLUOROANISOLE(452-09-5)
• EPA Substance Registry System: 4-CHLORO-2-FLUOROANISOLE(452-09-5)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• RIDADR: 1993
• WGK Germany: 3
• Hazardous Substances Data: 452-09-5(Hazardous Substances Data)

Usage

General Description

4-CHLORO-2-FLUOROANISOLE is a chemical compound that is also known as 2-fluoro-4-chloroanisole. It is a colorless to light yellow liquid with a sweet, aromatic odor. This chemical is used as an intermediate in the production of pharmaceuticals, agrochemicals, and other organic compounds. It is also used as a flavor and fragrance ingredient in the perfume industry. 4-CHLORO-2-FLUOROANISOLE is considered to be a potentially hazardous substance and should be handled with care, as it may cause irritation to the skin, eyes, and respiratory system if not properly managed.

InChI:InChI=1/C7H6ClFO/c1-10-7-3-2-5(8)4-6(7)9/h2-4H,1H3

Upstream product

• 366-99-4 3-fluoro-4-methoxyaniline 
• 95-03-4 5-chloro-2-methoxyaniline 
• 321-28-8 1-fluoro-2-methoxybenzene 
• 623-12-1 4-chloromethoxybenzene 
• 4274-03-7 2-methoxy-5-chloro-aniline-hydrochloride 

Downstream Products

• 348-62-9 4-chloro-2-fluorophenol 
• 112641-64-2 2-chloro-6-fluoro-5-methoxybenzaldehyde 
• 326-75-0 2-(4-chloro-2-fluorophenoxy)acetic acid 
• 867333-04-8 (6-chloro-2-fluoro-3-methoxyphenyl) boronic acid 
• 886499-58-7 6-chloro-2-fluoro-3-methoxy-benzoic acid 
• 91659-28-8 6-chloro-2-fluoro-3-hydroxy-benzoic acid 
• 1308662-42-1 2-(3-{[(6-Chloro-2-fluoro-3-methoxy-benzyl)-((S)-1 dimethylaminomethyl-3,3-dimethyl-butyl)-amino]-methyl}-benzyl)-1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid 
• 1308662-17-0 2-(3-{[(6-Chloro-2-fluoro-3-methoxy-benzyl)-((S)-1-dimethylaminomethyl-3,3-dimethyl-butyl)-amino]-methyl}-benzyl)-1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid ethyl ester 
• 1308662-44-3 2-(3-{[(6-chloro-2-fluoro-3-methoxy-benzyl)-((S)-1-dimethylaminomethyl-3,3-dimethyl-butyl)-amino]-methyl}-5-dimethylamino-benzyl)-1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid ethyl ester 
• 1308661-78-0 2-(3-{[(6-chloro-2-fluoro-3-methoxy-benzyl)-((S)-1-dimethylaminomethyl-3,3-dimethyl-butyl)-amino]-methyl}-benzyl)-1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid((1R,2R,3R,5S)-2,6,6-trimethyl-bicyclo[3.1.1]hept-3-yl)-amide 
• 1308661-80-4 2-(3-{[(6-chloro-2-fluoro-3-methoxy-benzyl)-((S)-1-dimethylaminomethyl-2-phenyl-ethyl)-amino]-methyl}-benzyl)-1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid ((1S,2S,3S,5R)-2,6,6-trimethyl-bicyclo[3.1.1]hept-3-yl)-amide 
• 1308661-81-5 2-[3-({(6-chloro-2-fluoro-3-methoxy-benzyl)-[(S)-2-(3-chloro-phenyl)-1-dimethylaminomethyl-ethyl]-amino}-methyl)-benzyl]-1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid((1S,2S,3S,5R)-2,6,6-trimethyl-bicyclo[3.1.1]hept-3-yl)-amide 
• 1308661-82-6 2-[3-({(6-chloro-2-fluoro-3-methoxy-benzyl)-[(S)-2-(4-chloro-phenyl)-1-dimethylaminomethyl-ethyl]-amino}-methyl)-benzyl]-1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid((1S,2S,3S,5R)-2,6,6-trimethyl-bicyclo[3.1.1]hept-3-yl)-amide 
• 1427406-96-9 1,3-bis(2-fluoro-6-methyl-3-triisopropylsilyloxyphenyl)urea 

Relevant articles and documents

Fluorination of aromatic compounds with N-fluorobenzenesulfonimide under solvent-free conditions

Reactions of N-fluorobenzenesulfonimide with methylbenzenes, phenols, and phenol ethers were studied under solvent-free conditions. The rate constant ratio for the reactions with mesitylene and durene indicates polar mechanism of the process. Solvent-free fluorination of aromatic compounds with N-fluorobenzenesulfonimide in some cases is more selective than reactions with other N-F reagents in a solvent.

First application of ionic liquids in electrophilic fluorination of arenes; Selectfluor (F-TEDA-BF4) for "green" fluorination

The NF fluorinating agent F-TEDA-BF4 dication salt (Selectfluor) 1 dissolves in imidazolium-based ionic liquids [emim][OTf] 7, [emim][BF4] 8, [bmim][PF6] 9 and [bmim][BF4] 10 (assisted by sonication), providing a convenient medium for fluorination of arenes under essentially acid-free conditions in a simple set-up (no volatile solvent; simple extraction of the aromatics without aqueous work-up), from which the ionic liquid can be easily recycled and reused. Comparative studies in [emim][OTf] 7 with anisole as substrate show that 1 is superior to NFTh-BF4 (Accufluor) 2 and that the N-fluoropyridinium salt NFPy-B2F7 4 is least effective. The scope of the reaction has been surveyed. Substrate selectivity (k mesitylene: k durene = 10) measured in competitive experiments in 7 is clearly indicative of a conventional polar mechanism. Substrate selectivity measured without the ionic liquid in MeCN solvent is also indicative of a polar mechanism but exhibits lower magnitude (k mesitylene: kdurene = 6). Addition of dicyclohexano-24-crown-8 to the fluorination reaction mixture (1 and anisole) in 7 reduced the conversion but did not change the isomer distribution. AM1 minimization was used to model the complexation of 1 with this crown. With reactive aromatics optimal fluorination yields in ionic liquids (using 1 equivalent of the NF reagent) are around 50% (higher for naphthalene). A key control experiment suggests that the free base (produced upon transfer-fluorination) could complex to unreacted 1 (generating a bulky dimer complex which may be ineffective for fluorine transfer) in competition to N-protonation.

Fluorination process

According to the present invention there is provided a process for the selective introduction of one or more fluorine atoms into a disubstituted aromatic compound in an acid medium with fluorine gas characterized in that the acid medium has a dielectric constant of at least 20 and a pH of less than 3. The present process provides a cost effective means of selectively introducing one or more fluorine atoms into an aromatic compound in good overall yield.