459-49-4

Usage

Physical state

Colorless liquid

Odor

Sweet, fruity

Uses

Intermediate in the production of pharmaceuticals and agrochemicals

Synthesis

Building block in the synthesis of various organic molecules

Chemical reactions

Halogenation, nitration, and Suzuki-Miyaura coupling

Safety

Harmful if swallowed or inhaled

Skin and eye contact

Can cause irritation

Aquatic life

Toxic to aquatic life

Handling and disposal

Proper precautions should be taken

Upstream product

• 873-75-6 4-bromobenzenemethanol 
• 19350-68-6 p-bromobenzaldehyde tosylhydrazone 
• 1620006-30-5 tetramethylammonium 1,1,2,2,3,3,3-heptafluoropropoxide 
• 589-15-1 1-bromomethyl-4-bromobenzene 
• 5467-74-3 4-Bromophenylboronic acid 
• 106-38-7 para-bromotoluene 
• 133745-75-2 N-fluorobis(benzenesulfon)imide 

Downstream Products

• 112088-75-2 6-chloro-9-(4-fluorobenzyl)purine 
• 132833-51-3 4-[(4-bromophenyl)methyl]morpholine 
• 1427555-68-7 1-[4-(fluoromethyl)phenyl]-3-(oxan-4-yl)-1H-pyrazolo[3,4-c]pyridine 
• 61692-92-0 1-p-Bromphenyl-3-p-tolylpropin-3 
• 2116-36-1 1-benzyl-4-bromo-benzene 
• 125486-45-5 9-(4-Fluoro-benzyl)-6-(furan-2-ylmethoxy)-9H-purine 
• 125486-46-6 9-(4-Fluoro-benzyl)-6-(pyridin-3-ylmethoxy)-9H-purine 
• 125486-44-4 6-Benzyloxy-9-(4-fluoro-benzyl)-9H-purine 
• 237763-11-0 methanesulfonic acid 4-bromo-benzyl ester 
• 101658-17-7 N-(4-bromobenzyl)-N-methylbenzenamine 
• 178162-69-1 1-(4-bromobenzyl)piperidine 

Relevant academic research and scientific papers

PROCESSES FOR FLUORINATION

The present technology relates to fluorination reactions. Specifically, processes useful for making the fungicide compound, DFT are disclosed. More broadly, also disclosed herein are processes useful for deoxyfluorination at the α-aromatic position of a given compound.

Copper-Catalyzed C-H Fluorination/Functionalization Sequence Enabling Benzylic C-H Cross Coupling with Diverse Nucleophiles

Site-selective transformation of benzylic C-H bonds into diverse functional groups is achieved via Cu-catalyzed C-H fluorination with N-fluorobenzenesulfonimide (NFSI), followed by substitution of the resulting fluoride with various nucleophiles. The benzyl fluorides generated in these reactions are reactive electrophiles in the presence of hydrogen-bond donors or Lewis acids, allowing them to be used without isolation in C-O, C-N, and C-C coupling reactions.

A Series of Deoxyfluorination Reagents Featuring OCF2Functional Groups

Research on perfluoroalkyl ether carboxylic acids (PFECAs) as alternatives for perfluoroalkyl substances continues with the goal of protecting the environment. However, very little is known about the utilization of decomposition products of PFECAs. We report herein a new series of deoxyfluorination reagents featuring OCF2 functional groups derived from certain PFECAs. Alkyl fluorides were generated from various alcohols in ≤97% yield by these novel reagents. The mechanistic experiment verified in situ generation of carbonic difluoride (COF2).

Fluorination reagent and deoxygenation fluorination method

In order to overcome the problems of high cost and poor stability of the existing deoxidation fluorination reagent, the invention provides a fluorination reagent. The fluorination reagent comprises acation M and an anion, and the anion is selected from one or more of the following perfluoropolyether chain carboxylic acid anions: CF3 (OCF2) nCO2, and n is selected from 1-10. Meanwhile, the invention further discloses a deoxidation fluorination method. The fluorination reagent provided by the invention has the advantages that the materials are easy to obtain, the fluorination products can beobtained at higher yield for various alcohol substrates, and the universality for different alcohol substrates is better.

Cobalt-Catalyzed Asymmetric Cross-Coupling Reaction of Fluorinated Secondary Benzyl Bromides with Lithium Aryl Boronates/ZnBr2

A cobalt-catalyzed asymmetric cross-coupling of α-bromo-α-fluorotoluene derivatives with a variety of aryl zincates derived from lithium aryl n-butyl pinacol boronates and ZnBr2 under mild reaction conditions was described. In addition to mild reaction conditions, another advantage includes the compatibility of various common functional groups such as fluoride, chloride, bromide, cyano, or ester groups. Furthermore, this protocol was successfully applied to the enantioselective synthesis of three fluorinated derivatives of biologically active compounds or drug molecules.

Thiourea-Catalyzed C?F Bond Activation: Amination of Benzylic Fluorides

We describe the first thiourea-catalyzed C?F bond activation. The use of a thiourea catalyst and Ti(OiPr)4 as a fluoride scavenger allows the amination of benzylic fluorides to proceed in moderate to excellent yields. Preliminary results with S- and O-based nucleophiles are also presented. DFT calculations reveal the importance of hydrogen bonds between the catalyst and the fluorine atom of the substrate to lower the activation energy during the transition state.

PROCESSES FOR FLUORINATION

The present technology relates to fluorination reactions. Specifically, processes useful for making the fungicide compound, DFT are disclosed. More broadly, also disclosed herein are processes useful for deoxyfluorination at the α-aromatic position of a given compound.

Nucleophilic Substitution of Aliphatic Fluorides via Pseudohalide Intermediates

A method for aliphatic fluoride functionalization with a variety of nucleophiles has been reported. Carbon–fluoride bond cleavage is thermodynamically driven by the use of silylated pseudohalides TMS-OMs or TMS-NTf2, resulting in the formation of TMS-F and a trapped aliphatic pseudohalide intermediate. The rate of fluoride/pseudohalide exchange and the stability of this intermediate are such that little rearrangement is observed for terminal fluoride positions in linear aliphatic fluorides. The ability to convert organofluoride positions into pseudohalide groups allows facile nucleophilic attack by a wide range of nucleophiles. The late introduction of the nucleophiles also allows for a wide range of functional-group tolerance in the coupling partners. Selective alkyl fluoride mesylation is observed in the presence of other alkyl halides, allowing for orthogonal synthetic strategies.

Nickel-catalyzed monofluoromethylation of aryl boronic acids

Aryl boronic acids can be monofluoromethylated under nickel catalysis. The utility of this method is demonstrated by the monofluoromethylation of a borylated and acyl-protected derivative of the statin drug ezetimibe. Mechanistic investigations indicate that a fluoromethyl radical is involved in the NiI/NiIII catalytic cycle.

A convenient route to tetraalkylammonium perfluoroalkoxides from hydrofluoroethers

Hydrofluoroethers are shown to alkylate tertiary amines readily under solvent-free conditions, affording valuable tetraalkylammonium perfluoroalkoxides bearing α-fluorines. The reaction of RFCF2-OCH3 (RF = CF2CF3, CF2CF2CF3, and CF(CF3)2) with NR1R2R3 produces twenty new α-perfluoroalkoxides, [(CH3)NR1R2R3][RFCF2O] under mild conditions. These α-perfluoroalkoxides are easy to handle, thermally stable, and can be used for the perfluoroalkoxylation of benzyl bromides.