3-Fluorophenylboronic acid, also known as 3-Fluorophenylboronic acid, is a white solid at room temperature and pressure, soluble in alcohol organic solvents and dimethyl sulfoxide, with a certain level of acidity. It is a type of phenylboronic acid compound that can be prepared by the Miyaura boronization reaction under the catalysis of transition metals using 3-Fluorobromobenzene as the starting material. It is mainly used as a pharmaceutical intermediate, allowing the introduction of the 3-Fluorophenyl group into the structure of functional organic molecules through boronic acid coupling reactions.

What are the physical and chemical properties of 3-Fluorophenylboronic acid?

3-Fluorophenylboronic acid exhibits general physical and chemical properties of phenylboronic acid. It is sensitive to oxidants and can be easily oxidized to corresponding phenol derivatives when in contact with sodium perborate or hydrogen peroxide. Its main application in organic synthesis chemistry is its cross-coupling reaction with aryl halides under the catalysis of palladium metal, which can be used for structural modification and preparation of drug molecules and pesticide chemicals.

How does the Suzuki coupling reaction of 3-Fluorophenylboronic acid work?

Figure 1 Suzuki coupling reaction of 3-Fluorophenylboronic acid

To a dry reaction flask, mix ortho-bromoaniline (5.0 mmol, 1 equivalent), 3-Fluorophenylboronic acid (7.5 mmol, 1.5 equivalents), diisopropylamine (10.0 mmol, 2 equivalents), Pd(OAc)2 (0.25 mol%, 2.8 mg), and H2O (10.0 mL), then vigorously stir the resulting reaction mixture at 100 °C for 30 minutes. Monitor the progress of the reaction by TLC plate, and after the reaction is complete, add the reaction mixture to 15 mL of saline water and extract the aqueous layer three times with ethyl acetate (3 × 20 mL). Dry and combine the organic layer on anhydrous MgSO4, filter the mixture under vacuum to remove the drying agent, concentrate the filtrate under vacuum, and finally purify the crude product by silica gel column chromatography to obtain the coupled product molecule.

What are the chemical applications of 3-Fluorophenylboronic acid?

3-Fluorophenylboronic acid is an important organic synthesis intermediate with wide applications in pharmaceutical chemistry and materials science. Its preparation method is relatively simple and efficient, and its chemical properties are stable. It can undergo coupling reactions with different organic molecules, providing important tools and material basis for research and applications in organic chemistry. Many drug molecules contain aryl groups in their structure, and by introducing 3-Fluorophenylboronic acid, structural modifications can be made to improve their pharmacological properties and enhance their efficacy and selectivity.

References

[1] Elsherbini, Mohamed; et al Organic & Biomolecular Chemistry (2021), 19(21), 4706-4711.