87453-27-8

Basic information

• Product Name: (fluoromethoxy)benzene
• Synonyms: (Fluoromethoxy)benzene; 87453-27-8; F1OR [WLN]; Fluoromethyl phenyl ether
• CAS NO: 87453-27-8
• Molecular Formula: C₇H₇FO
• Molecular Weight: 126.1283
• Mol File: 87453-27-8.mol

Chemical Properties

• Boiling Point: 154.8°C at 760 mmHg
• Flash Point: 50.9°C
• Density: 1.06g/cm³
• Vapor Pressure: 4.01mmHg at 25°C
• Refractive Index: 1.468
• CAS DataBase Reference: (fluoromethoxy)benzene(CAS DataBase Reference)
• NIST Chemistry Reference: (fluoromethoxy)benzene(87453-27-8)
• EPA Substance Registry System: (fluoromethoxy)benzene(87453-27-8)

Safety Data

• Hazardous Substances Data: 87453-27-8(Hazardous Substances Data)

Usage

Uses

Used in Organic Synthesis:
(Fluoromethoxy)benzene is utilized as a building block in organic synthesis, contributing to the creation of a wide range of chemical compounds due to its reactive nature and structural properties.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, (fluoromethoxy)benzene is used as an intermediate in the synthesis of various drugs, leveraging its chemical reactivity to form complex molecular structures that can exhibit therapeutic effects.
Used in Agrochemical Industry:
Similarly, in the agrochemical industry, (fluoromethoxy)benzene serves as an intermediate in the production of pesticides and other agricultural chemicals, where its chemical properties are harnessed to create effective compounds for crop protection and enhancement.
Used as a Solvent in Research Laboratories:
(Fluoromethoxy)benzene is also employed as a solvent in research laboratories, where its ability to dissolve a variety of substances makes it useful in conducting experiments and facilitating chemical reactions.
Used as a Reagent in Research Laboratories:
Furthermore, it functions as a reagent in research settings, participating directly in chemical reactions to help scientists investigate and understand various organic processes and syntheses.
It is crucial to handle (fluoromethoxy)benzene with care due to its potential hazards to human health and the environment, emphasizing the need for proper safety measures during its use in various applications.

Upstream product

• 100-51-6 benzyl alcohol 
• 122-59-8 2-phenoxyacetic acid 
• 6707-01-3 (chloromethoxy)benzene 
• 33837-96-6 methyl thiomethyl ether of phenol 
• 39213-29-1 ((methylsulfinyl)methoxy)benzene 
• 373-53-5 fluoroiodomethane 
• 108-95-2 phenol 
• 5789-77-5 tert-butyl 2-phenoxyethaneperoxoate 
• 133745-75-2 N-fluorobis(benzenesulfon)imide 
• 139-02-6 sodium phenoxide 
• 2555-49-9 phenoxyacetic acid ethyl ester 
• 593-70-4 R₃₂ 

Downstream Products

• 2050-04-6 (pentyloxy)benzene 
• 1746-13-0 allyl phenyl ether 

Relevant articles and documents

Metal-free electrochemical fluorodecarboxylation of aryloxyacetic acids to fluoromethyl aryl ethers

Electrochemical decarboxylation of aryloxyacetic acids followed by fluorination provides easy access to fluoromethyl aryl ethers. This electrochemical fluorodecarboxylation offers a sustainable approach with electric current as traceless oxidant. Using Et3N·5HF as fluoride source and as supporting electrolyte, this simple electrosynthesis affords various fluoromethoxyarenes in yields up to 85%.

Continuous Heterogeneous Photocatalysis in Serial Micro-Batch Reactors

Solid reagents, leaching catalysts, and heterogeneous photocatalysts are commonly employed in batch processes but are ill-suited for continuous-flow chemistry. Heterogeneous catalysts for thermal reactions are typically used in packed-bed reactors, which cannot be penetrated by light and thus are not suitable for photocatalytic reactions involving solids. We demonstrate that serial micro-batch reactors (SMBRs) allow for the continuous utilization of solid materials together with liquids and gases in flow. This technology was utilized to develop selective and efficient fluorination reactions using a modified graphitic carbon nitride heterogeneous catalyst instead of costly homogeneous metal polypyridyl complexes. The merger of this inexpensive, recyclable catalyst and the SMBR approach enables sustainable and scalable photocatalysis.

Fluorine in drug design: A case study with fluoroanisoles

Anisole and fluoroanisoles display distinct conformational preferences, as evident from a survey of their crystal structures. In addition to altering the free ligand conformation, various degrees of fluorination have a strong impact on physicochemical and pharmacokinetic properties. Analysis of anisole and fluoroanisole matched molecular pairs in the Pfizer corporate database reveals interesting trends: 1) PhOCF3 increases log D by ～1 log unit over PhOCH3 compounds; 2) PhOCF3 shows lower passive permeability despite its higher lipophilicity; and 3) PhOCF3 does not appreciably improve metabolic stability over PhOCH3. Emerging from the investigation, difluoroanisole (PhOCF2H) strikes a better balance of properties with noticeable advantages of log D and transcellular permeability over PhOCF3. Synthetic assessment illustrates that the routes to access difluoroanisoles are often more straightforward than those for trifluoroanisoles. Whereas replacing PhOCH3 with PhOCF3 is a common tactic to optimize ADME properties, our analysis suggests PhOCF2H may be a more attractive alternative, and greater exploitation of this motif is recommended.

Radical decarboxylative fluorination of aryloxyacetic acids using N-fluorobenzenesulfonimide and a photosensitizer

Fluorinated methoxy arenes are emerging as important motifs in both agrochemicals and pharmaceuticals. A novel technique for the synthesis of monofluoromethoxy arenes through the direct fluorodecarboxylation of carboxylic acids was developed that uses photosensitizers and N-fluorobenzenesulfonimide (NFSI). Utilization of the oxidatively mild fluorine transfer agent NFSI enabled the synthesis of fluoromethyl ethers that were previously inaccessible with decarboxylative fluorinations performed with Selectfluor. Mechanistic studies are consistent with the photosensitizer effecting oxidation of the aryloxyacetic acid.

Direct C-F bond formation using photoredox catalysis

We have developed the first example of a photoredox catalytic method for the formation of carbon-fluorine (C-F) bonds. The mechanism has been studied using transient absorption spectroscopy and involves a key single-electron transfer from the 3MLCT (triplet metal-to-ligand charge transfer) state of Ru(bpy)32+ to Selectfluor. Not only does this represent a new reaction for photoredox catalysis, but the mild reaction conditions and use of visible light also make it a practical improvement over previously developed UV-mediated decarboxylative fluorinations.

Direct monofluoromethylation of O-, S-, N-, and P-nucleophiles with PhSO(NTs)CH2F: The accelerating effect of α-fluorine substitution

An efficient and direct monofluoromethylation of O-, S-, N-, and P-nucleophiles with PhSO(NTs)CH2F 1 has been developed. In contrast to the previously known detrimental effect of α-fluorine substitution on SN2 reactions, the current monofluoromethylation is accelerated by the α-fluorine substitution. Based on a mechanistic study, a new reactivity of sulfoximine (as a radical monofluoromethylation reagent) is disclosed.

Photo-fluorodecarboxylation of 2-aryloxy and 2-aryl carboxylic acids

Coming to light: The title reaction simply requires an aqueous alkaline solution of Selectfluor and light. The method is inexpensive and effective for a wide range of neutral and electron-poor 2-aryloxy and 2-aryl acetic acids to provide fluoromethyl ethers (see scheme) and benzyl fluorides, respectively. The mechanism most likely proceeds through an initial aryl excitation with a subsequent single-electron transfer. Copyright

Fluorine transfer to alkyl radicals

The development of new synthetic technologies for the selective fluorination of organic compounds has increased with the escalating importance of fluorine-containing pharmaceuticals. Traditional methods potentially applicable to drug synthesis rely on the use of ionic forms of fluorine (F - or F+). Radical methods, while potentially attractive as a complementary approach, are hindered by a paucity of safe sources of atomic fluorine (F?). A new approach to alkyl fluorination has been developed that utilizes the reagent N-fluorobenzenesulfonimide as a fluorine transfer agent to alkyl radicals. This approach is successful for a broad range of alkyl radicals, including primary, secondary, tertiary, benzylic, and heteroatom-stabilized radicals. Furthermore, calculations reveal that fluorine-containing ionic reagents are likely candidates for further expansion of this approach to polar reaction media. The use of these reagents in alkyl radical fluorination has the potential to enable powerful new transformations that otherwise would take multiple synthetic steps.

Oxidation of benzyl alcohols with difluoro(aryl)-λ3-bromane: formation of benzyl fluoromethyl ethers via oxidative rearrangement

Oxidative rearrangement of benzyl alcohols with difluoro(p-trifluoromethylphenyl)-λ3-bromane (5 × 10-2 M) in chloroform at room temperature afforded aryl fluoromethyl ethers selectively in good yields, probably via 1,2-shift of aryl groups from benzylic carbon to oxygen atoms.

Electrophilic monofluoromethylation of O-, S-, and N-nucleophiles with chlorofluoromethane

CH2ClF has been found to be a useful electrophilic monofluoromethylating agent for a variety of O-, S-, and N-nucleophiles. The reaction is not sensitive to the radical scavenger such as nitrobenzene, which strongly supports an SN2 m