459-57-4 | 4-Fluorobenzaldehyde

CAS:459-57-4 | 4-Fluorobenzaldehyde,Description

4-Fluorobenzaldehyde is a chemical compound that has been the subject of various studies due to its interesting properties and potential applications. It is characterized by the presence of a fluorine atom attached to a benzene ring, which is also connected to an aldehyde group. This structure imparts unique physical and chemical characteristics to the molecule, making it a valuable compound in different fields of chemistry and materials science.

Synthesis Analysis

The synthesis of 4-fluorobenzaldehyde has been explored through several methods. A common approach involves the halogen-exchange fluorination reaction, where 4-chlorobenzaldehyde is converted to 4-fluorobenzaldehyde using potassium fluoride in the presence of tetraphenylphosphonium halide and 18-crown-6 or polyethylene glycol dimethyl ether as catalysts. This method has been optimized to achieve high yields and purity, with a reported yield of 80.9% and a purity of 99.5% under optimal conditions. Additionally, an automated synthesis procedure has been developed for the production of 4-[18F]fluorobenzaldehyde, which is used as a prosthetic group for amino-oxy functionalized peptide labeling in clinical applications.

Molecular Structure Analysis

The molecular structure of 4-fluorobenzaldehyde has been extensively studied. Gas electron diffraction, microwave spectroscopy, and ab initio molecular orbital calculations have all been employed to determine the structure of the gaseous form of the molecule. These studies have confirmed that 4-fluorobenzaldehyde has a planar Cs symmetry structure, with specific bond lengths measured for the carbon-fluorine and carbon-oxygen bonds. The rotational spectrum of the molecule has also been investigated, providing insights into its planarity and the energy levels of its torsional states.

Chemical Reactions Analysis

4-Fluorobenzaldehyde participates in various chemical reactions due to its aldehyde functional group. It can undergo nucleophilic substitution with amines to form 4-aminobenzaldehydes, which can then react with hydrazides to yield hydrazones. The compound has also been used as a starting material for the synthesis of fluorinated phenols, such as 4-fluoroguaiacol and 4-fluorocatechol, through nucleophilic aromatic substitution followed by Baeyer-Villiger oxidation.

Physical and Chemical Properties Analysis

The physical and chemical properties of 4-fluorobenzaldehyde have been characterized through various spectroscopic techniques. The presence of C-H...O hydrogen bonds in the liquid phase has been supported by vibrational and NMR spectroscopy, with particular attention to the effects on the C-H stretching region. The molecule's dipole moment components and rotational parameters have been derived from its microwave spectrum, which also indicates that the molecule is planar.

Scientific Research Applications

Synthesis Methods

• 4-Fluorobenzaldehyde is synthesized from 4-chlorobenzaldehyde using potassium fluoride, tetraphenylphosphonium halide, and 18-crown-6 or poly(ethylene glycol) dimethyl ether, yielding several fluorobenzaldehyde derivatives in good yields (Yoshida & Kimura, 1988).
• An alternative synthesis process for large quantities of 4-fluorobenzaldehyde involves halogen-exchange of 4-chlorobenzaldehyde with potassium fluoride in aromatic hydrocarbon solvents (Yoshida & Kimura, 1989).

Chemical Properties and Analysis

• The presence of C-H...O hydrogen bonds in liquid 4-fluorobenzaldehyde has been studied using ab initio calculations and spectroscopic methods. The bonds' energies, geometries, and spectroscopic properties were analyzed (Ribeiro-Claro, Marques, & Amado, 2002).
• The molecular structure of gaseous 4-fluorobenzaldehyde was determined by joint analysis of gas electron diffraction data, microwave spectroscopy, and ab initio calculations (Samdal et al., 1997).

Applications in Synthesis of Other Compounds

• 4-Fluorobenzaldehyde has been used for preparing 2-(4-fluorophenyl)thiazolidin-4-one derivatives, which show promising antioxidant activity (El Nezhawy et al., 2009).
• It is also involved in the sonochemical nucleophilic aromatic substitutions with different azacycloalkanes and azoles, showing a beneficial ultrasound effect (Magdolen, Mečiarová, & Tomá, 2001).

Advanced Applications

• 4-Fluorobenzaldehyde is used as a prosthetic group for amino-oxy functionalized peptide labeling in clinical routine applications, highlighting its role in medical research (Speranza et al., 2009).
• Its utilization in creating fluorinated microporous polyaminals demonstrates potential for carbon dioxide adsorption, a key area in environmental chemistry (Li, Zhang, & Wang, 2016).

Safety And Hazards

4-Fluorobenzaldehyde is a flammable liquid and vapour. It causes skin irritation and serious eye irritation. It may cause respiratory irritation. It is advised to avoid dust formation, avoid breathing mist, gas or vapours, avoid contacting with skin and eye, use personal protective equipment, wear chemical impermeable gloves, ensure adequate ventilation, remove all sources of ignition, evacuate personnel to safe areas, and keep people away from and upwind of spill/leak.

Future Directions

Fluorobenzaldehyde can be used as a synthetic intermediate because the fluorine can be replaced via oxidation reaction. Due to the aldehyde group, the fluorobenzaldehydes can be used to make a variety of Schiff base compounds through a condensation reaction. Schiff bases containing halogenated aromatic rings exhibit antimicrobial properties. A new three-component condensation of β-ketonitriles, 4-fluorobenzaldehyde, and secondary cyclic amines was developed. This could open up new avenues for the synthesis of complex molecules.

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