4-Fluorophenylmagnesium bromide
[CAS# 352-13-6]

Identification

• Classification: Organic raw materials >> Organometallic compound >> Organomagnesium
• Name: 4-Fluorophenylmagnesium bromide
• Molecular Formula: C₆H₄BrFMg
• Molecular Weight: 199.30
• CAS Registry Number: 352-13-6
• EC Number: 627-087-3
• SMILES: C1=CC(=CC=[C-]1)F.[Mg+2].[Br-]

Properties

• Density: 1.021 g/mL (25 °C)
• Flash point: -20 °C (closed cup)

Safety Data

• Hazard Symbols: GHS02;GHS05 Danger
• Risk Statements: H225-H314-H318-H412
• Safety Statements: P210-P233-P240-P241-P242-P243-P260-P264-P264+P265-P273-P280-P301+P330+P331-P302+P361+P354-P303+P361+P353-P304+P340-P305+P354+P338-P316-P317-P321-P363-P370+P378-P403+P235-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin corrosion	Skin Corr.	1B	H314
Serious eye damage	Eye Dam.	1	H318
Flammable liquids	Flam. Liq.	2	H225
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412

• Transport Information: UN 2924 3/PG 2

Discovery and Applications

4-Fluorophenylmagnesium bromide is an organomagnesium compound belonging to the class of Grignard reagents. This chemical compound is widely used in organic synthesis due to its reactivity and ability to form carbon-carbon bonds, making it a valuable tool in the preparation of various pharmaceuticals, agrochemicals, and materials.

The discovery of 4-fluorophenylmagnesium bromide is closely tied to the development of Grignard reagents, which were first synthesized by the French chemist Victor Grignard in the early 20th century. Grignard's work led to the development of a wide range of organomagnesium compounds, which have since become essential in organic chemistry for their ability to form nucleophilic carbon-magnesium bonds. The specific synthesis of 4-fluorophenylmagnesium bromide involves the reaction of 4-fluorobromobenzene with magnesium metal in anhydrous ether, under an inert atmosphere, to form the Grignard reagent.

4-Fluorophenylmagnesium bromide finds applications in various synthetic routes, particularly in the synthesis of aryl fluorides and other complex organic molecules. Its primary utility lies in its ability to react with electrophiles, such as carbonyl compounds, esters, or halides, forming new carbon-carbon bonds. This makes it a crucial intermediate in the synthesis of a wide range of pharmaceuticals and fine chemicals. For example, it has been used in the preparation of 4-fluorophenyl ketones, aldehydes, and alcohols, which are important intermediates in drug development.

Additionally, 4-fluorophenylmagnesium bromide is an essential reagent in the synthesis of aromatic compounds with fluorine substituents. The incorporation of the fluorine atom into aromatic systems can significantly alter the physical, chemical, and biological properties of the resulting compounds, making them more suitable for specific applications, including those in medicinal chemistry. Fluorine substitution is known to improve the metabolic stability, bioavailability, and binding affinity of drugs, which is why 4-fluorophenylmagnesium bromide plays a key role in the pharmaceutical industry.

In addition to its use in pharmaceuticals, 4-fluorophenylmagnesium bromide is also employed in the production of materials and agrochemicals. For example, it is used in the synthesis of fluorescent dyes, liquid crystals, and organic semiconductors, where its ability to introduce fluorine into aromatic systems is particularly beneficial for improving the electronic properties of the materials.

The reactivity of 4-fluorophenylmagnesium bromide also makes it an excellent tool in the field of materials science, particularly in the development of organic electronics. Its ability to form stable bonds with a variety of electrophiles has allowed researchers to create advanced functional materials, such as organic light-emitting diodes (OLEDs) and organic photovoltaic cells (OPVs), where fluorine plays a crucial role in enhancing the stability and performance of these devices.

The synthesis of 4-fluorophenylmagnesium bromide requires careful control of reaction conditions, including the use of anhydrous solvents and the maintenance of an inert atmosphere to prevent unwanted reactions with moisture or oxygen. This careful preparation ensures the reagent is reactive enough to participate in synthetic transformations without decomposing or undergoing side reactions.

References

2021. Grignard Reagents in Organic Synthesis. Organic Process Research & Development, 25(7).
DOI: 10.1021/acs.oprd.1c00123