352-33-0

Basic information

• Product Name: 1-Chloro-4-fluorobenzene
• Synonyms: 4-FLUOROCHLOROBENZENE;4-CHLOROFLUOROBENZENE;1,4-Fluorochlorobenzene;1-chloro-4-fluoro-benzen;1-Fluoro-4-chlorobenzene;P-FLUOROCHLOROBENZENE;P-CHLOROFLUOROBENZENE;4-CHLOROFLUOROBENZENE 99% (GC)
• CAS NO: 352-33-0
• Molecular Formula: C₆H₄ClF
• Molecular Weight: 130.55
• EINECS: 206-521-1
• Product Categories: Aromatic Hydrocarbons (substituted) & Derivatives;Chlorine Compounds;Fluorine Compounds;Fluoro;Aryl;C6;Halogenated Hydrocarbons;Gasoline, Diesel, Petroleum;Alpha Sort;C;CAlphabetic;CHChemical Class;Environmental Standards;FluoroEPA;Gasoline Range organics (GRO)Chromatography;Halogenated;UST/GRO/DRO;Volatiles/ Semivolatiles;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;alkyl Fluorine| alkyl chloride
• Mol File: 352-33-0.mol

Chemical Properties

• Melting Point: -21.5 °C
• Boiling Point: 129-130 °C(lit.)
• Flash Point: 85 °F
• Appearance: Clear colorless to slightly yellow/Liquid
• Density: 1.226 g/mL at 25 °C(lit.)
• Vapor Pressure: 1.04mmHg at 25°C
• Refractive Index: n20/D 1.495(lit.)
• Storage Temp.: Flammables area
• Solubility: Difficult to mix.
• BRN: 1904542
• CAS DataBase Reference: 1-Chloro-4-fluorobenzene(CAS DataBase Reference)
• NIST Chemistry Reference: 1-Chloro-4-fluorobenzene(352-33-0)
• EPA Substance Registry System: 1-Chloro-4-fluorobenzene(352-33-0)

Safety Data

• Hazard Codes: Xi,F,T
• Statements: 10-36/37/38-39/23/24/25-23/24/25-11
• Safety Statements: 16-26-36-37/39-45-36/37-7
• RIDADR: UN 1993 3/PG 3
• WGK Germany: 3
• TSCA: T
• HazardClass: 3
• PackingGroup: III
• Hazardous Substances Data: 352-33-0(Hazardous Substances Data)

Usage

Uses

1. Used in Organic Synthesis:
1-Chloro-4-fluorobenzene is used as a primary and secondary intermediate in organic synthesis. Its unique combination of chlorine and fluorine atoms on the benzene ring makes it a versatile building block for the creation of various complex organic molecules. The presence of these halogens allows for further functionalization and modification of the molecule, enabling the synthesis of a wide range of compounds with diverse applications.
2. Used in Pharmaceutical Industry:
In the pharmaceutical industry, 1-Chloro-4-fluorobenzene is employed as a key intermediate for the synthesis of various active pharmaceutical ingredients (APIs). Its reactivity and structural properties make it suitable for the development of new drugs with improved efficacy and selectivity. 1-Chloro-4-fluorobenzene can be further modified to introduce functional groups that can interact with specific biological targets, leading to the development of novel therapeutic agents.
3. Used in Chemical Intermediates for Diverse Applications:
1-Chloro-4-fluorobenzene is also used as a chemical intermediate for the production of various compounds with applications in different industries. For instance, it can be used to prepare (4'-fluoro-biphenyl-4-yl)-methyl ether, a compound with potential applications in the field of materials science. The synthesis of this compound involves the use of reagents such as NaH, Ni(OAc)2, 2,2'-bipyridyl, KI, and solvents like benzene and tetrahydrofuran at a temperature of 63°C.
4. Used in the Production of Specialty Materials:
The unique properties of 1-Chloro-4-fluorobenzene make it an attractive candidate for the development of specialty materials with specific characteristics. For example, its halogenated nature allows for the creation of materials with enhanced thermal stability, chemical resistance, and electrical properties. These materials can find applications in various industries, such as electronics, aerospace, and automotive, where high-performance materials are required.

InChI:InChI=1/C6H4FI/c7-5-1-3-6(8)4-2-5/h1-4H

Upstream product

• 1582-27-0 4-chlorobenzene-diazonium hexafluorophosphate 
• 462-06-6 fluorobenzene 
• 541-73-1 1,3-Dichlorobenzene 
• 1679-18-1 4-Chlorophenylboronic acid 
• 195062-61-4 4-chlorophenylboronic acid pinacol ester 
• 108-90-7 chlorobenzene 
• 14064-15-4 (4-chlorophenyl)trimethylstannane 
• 1644-73-1 4-chlorophenyl fluoroformate 
• 358-23-6 trifluoromethylsulfonic anhydride 
• 673-41-6 p-chlorobenzenediazonium tetrafluoroborate 
• 106-46-7 para-dichlorobenzene 
• 371-41-5 4-Fluorophenol 
• 371-40-4 4-fluoroaniline 
• 188290-36-0 thiophene 

Downstream Products

• 92-88-6 4,4'-Dihydroxybiphenyl 
• 324-94-7 4'-fluoro-biphenyl-4-ol 
• 398-23-2 4,4'-difluorobiphenyl 
• 462-06-6 fluorobenzene 
• 456-22-4 4-Fluorobenzoic acid 
• 394-30-9 5-chloro-2-fluorobenzoic acid 
• 2252-50-8 2-chloro-5-fluoro-benzoic acid 
• 350-40-3 2-(4-fluorophenyl)-1-propene 
• 1836-74-4 4-(4-chlorophenoxy)nitrobenzene 
• 333954-83-9 tert-butyl 4-(4-chlorophenoxy)piperidine-1-carboxylate 
• 4280-36-8 (4-fluorophenyl)piperidine 
• 96515-79-6 5-chloro-2-fluorobenzaldehyde 
• 447460-31-3 C₁₂H₇ClF₂O₂S 
• 1037412-73-9 1-benzyl-5-(4-fluorophenyl)-4-phenyl-1H-1,2,3-triazole 

Relevant articles and documents

Photocatalytic monofluorination of benzene by fluoride via photoinduced electron transfer with 3-cyano-1-methylquinolinium

The photocatalytic fluorination of benzene occurs under photoirradiation of an oxygen-saturated acetonitrile (MeCN) of the 3-cyano-1-methylquinolinium ion (QuCN+) containing benzene and tetraethylammonium fluoride tetrahydrofluoride (TEAF·4HF) with a xenon lamp (500 W) attached to a colored-glass filter (λ + and benzene exhibited absorption bands due to QuCN ? (λmax = 500 nm) and the benzene dimer radical cation (λmax = 900 nm), which were generated by photoinduced electron transfer from benzene to the singlet excited state of QuCN+. The decay rate of the transient absorption band due to the benzene dimer radical cation was accelerated by the addition of TEAF·4HF. The observed rate constant increased with increasing concentration of TEAF·4HF. The rate constant of the electrophilic addition of fluoride to the benzene radical cation was determined to be 9.4 × 109 M-1 s-1. Thus, the photocatalytic reaction is initiated by intermolecular photoinduced electron transfer from benzene to the single excited state of QuCN+. The benzene radical cation formed by photoinduced electron transfer reacts with the fluoride anion to yield the F-adducted radical. However, QuCN? can reduce O2 to O2?-, and this is followed by the protonation of O2?- to afford HO2?. The hydrogen abstraction of HO2? from the F-adduct radical affords fluorobenzene and H2O2 as the final products.

Nucleophilic Fluorination of Heteroaryl Chlorides and Aryl Triflates Enabled by Cooperative Catalysis

Aryl and heteroaryl fluorides are growing to be dominant motifs in pharmaceuticals and agrochemicals, yet they are rare in both nature and commodity chemicals. As a consequence, there is an increasingly urgent need to develop mild, cost-effective, and scalable methods for fluorination. The most straightforward route to synthesize aryl fluorides is through the halide exchange "halex"reaction, but conditions, cost, and atom economy preclude most available methods from large-scale manufacturing processes. We report a new approach that leverages the cooperative action of 18-crown-6 ether and tetramethylammonium chloride to catalytically access the reactivity of tetramethylammonium fluoride and achieve halex fluorinations under mild conditions with operational ease. The described methodology readily converts both heteroaryl chlorides and aryl triflates to their corresponding (hetero)aryl fluorides in high yields and purities.

Fluorination of arylboronic esters enabled by bismuth redox catalysis

Bismuth catalysis has traditionally relied on the Lewis acidic properties of the element in a fixed oxidation state. In this paper, we report a series of bismuth complexes that can undergo oxidative addition, reductive elimination, and transmetallation in a manner akin to transition metals. Rational ligand optimization featuring a sulfoximine moiety produced an active catalyst for the fluorination of aryl boronic esters through a bismuth (III)/bismuth (V) redox cycle. Crystallographic characterization of the different bismuth species involved, together with a mechanistic investigation of the carbonfluorine bond-forming event, identified the crucial features that were combined to implement the full catalytic cycle.

Highly efficient Sandmeyer reaction on immobilized CuI/CuII-based catalysts

Highly effective embodiment of Sandmeyer reaction has been revealed for Cu-based catalysts incorporating ionic liquid on Silochrom support. The most active catalyst (TOF = = 4000–8000 h–1) contains comparable amounts of cuprous and cupric chloride anions. The reported method allows one to carry out the reaction for anilines in the one-pot mode.

Palladium-catalysed electrophilic aromatic C-H fluorination

Aryl fluorides are widely used in the pharmaceutical and agrochemical industries, and recent advances have enabled their synthesis through the conversion of various functional groups. However, there is a lack of general methods for direct aromatic carbon-hydrogen (C-H) fluorination. Conventional methods require the use of either strong fluorinating reagents, which are often unselective and difficult to handle, such as elemental fluorine, or less reactive reagents that attack only the most activated arenes, which reduces the substrate scope. A method for the direct fluorination of aromatic C-H bonds could facilitate access to fluorinated derivatives of functional molecules that would otherwise be difficult to produce. For example, drug candidates with improved properties, such as increased metabolic stability or better blood-brain-barrier penetration, may become available. Here we describe an approach to catalysis and the resulting development of an undirected, palladium-catalysed method for aromatic C-H fluorination using mild electrophilic fluorinating reagents. The reaction involves a mode of catalysis that is unusual in aromatic C-H functionalization because no organometallic intermediate is formed; instead, a reactive transition-metal-fluoride electrophile is generated catalytically for the fluorination of arenes that do not otherwise react with mild fluorinating reagents. The scope and functional-group tolerance of this reaction could provide access to functional fluorinated molecules in pharmaceutical and agrochemical development that would otherwise not be readily accessible.

Reactions of Arylsulfonate Electrophiles with NMe4F: Mechanistic Insight, Reactivity, and Scope

This paper describes a detailed study of the deoxyfluorination of aryl fluorosulfonates with tetramethylammonium fluoride (NMe4F) and ultimately identifies other sulfonate electrophiles that participate in this transformation. 19F NMR spectroscopic monitoring of the deoxyfluorination of aryl fluorosulfonates revealed the rapid formation of diaryl sulfates under the reaction conditions. These intermediates can proceed to fluorinated products; however, diaryl sulfate derivatives bearing electron-donating substituents react very slowly with NMe4F. Based on these findings, aryl triflate and aryl nonaflate derivatives were explored, since these cannot react to form diaryl sulfates. Aryl triflates were found to be particularly effective electrophiles for deoxyfluorination with NMe4F, and certain derivatives (i.e., those bearing electron-neutral/donating substituents) afforded higher yields than their aryl fluorosulfonate counterparts. Computational studies implicate a similar mechanism for deoxyfluorination of all the sulfonate electrophiles.

PROCESS FOR THE PREPARATION OF ORGANIC HALIDES

The present invention provides a halo-de-carboxylation process for the preparation of organic chlorides, organic bromides and mixtures thereof, from their corresponding carboxylic acids, using a chlorinating agent selected from trichloroisocyanuric acid (TCCA), dichloroisocyanuric acid (DCCA), or combination thereof, and a brominating agent.

METHOD FOR AROMATIC FLUORINATION

Disclosed is a fluorination method comprising providing an aryl fluorosuifonate and a fluorinating reagent to a reaction mixture; and reacting the aryl fluorosuifonate and the fluorinating reagent to provide a fluorinated aryl species. Also disclosed is a fluorination method comprising providing, a salt comprising a cation and an aryloxyiate, and SO2F2 to a reaction mixture; reacting the SO2F2 and the ammonium salt to provide a fluorinated aryl species. Further disclosed a fluorination method comprising providing a compound having the structure Ar-OH to a reaction mixture; where A is an aryl or heteroaryl; providing SO2F2 to the reaction mixture; providing a fluorinating reagent to the reaction mixture; reacting the SO2F2, the fluorinating reagent and the compound having the structure Ar-OH to provide a fluorinated aryl species having the structure Ar-F.

DIRECT PALLADIUM-CATALYZED AROMATIC FLUORINATION

Provided herein are palladium complexes comprising a ligand of Formula (Α') and a ligand of Formula (B), wherein R1-R18 are as defined herein. The palladium complexes are useful in methods of fluorinating aryl and heteroaryl substrates. Further provided are compositions and kits comprising the palladium complexes.

Nucleophilic deoxyfluorination of phenols via aryl fluorosulfonate intermediates

This report describes a method for the deoxyfluorination of phenols with sulfuryl fluoride (SO2F2) and tetramethylammonium fluoride (NMe4F) via aryl fluorosulfonate (ArOFs) intermediates. We first demonstrate that the reaction of ArOFs with NMe4F proceeds under mild conditions (often at room temperature) to afford a broad range of electronically diverse and functional group-rich aryl fluoride products. This transformation was then translated to a one-pot conversion of phenols to aryl fluorides using the combination of SO2F2 and NMe4F. Ab initio calculations suggest that carbon-fluorine bond formation proceeds via a concerted transition state rather than a discrete Meisenheimer intermediate.