3-Chloro-2-fluorobenzaldehyde
[CAS# 85070-48-0]

Identification

• Classification: Organic raw materials >> Organic fluorine compound >> Fluorobenzaldehyde series
• Name: 3-Chloro-2-fluorobenzaldehyde
• Molecular Formula: C₇H₄ClFO
• Molecular Weight: 158.55
• CAS Registry Number: 85070-48-0
• EC Number: 617-667-4
• SMILES: C1=CC(=C(C(=C1)Cl)F)C=O

Properties

• Density: 1.4±0.1 g/cm³, Calc.^*, 1.35 g/mL (Expl.)
• Index of Refraction: 1.56, Calc.^*, 1.545 (Expl.)
• Boiling Point: 213.9±20.0 °C (760 mmHg), Calc.^*, 214 °C (Expl.)
• Flash Point: 83.2±21.8 °C, Calc.^*, 86 °C (Expl.)

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2	H319
Eye irritation	Eye Irrit.	2A	H319
Flammable liquids	Flam. Liq.	4	H227

Discovery and Applications

3-Chloro-2-fluorobenzaldehyde is an aromatic aldehyde that contains both chlorine and fluorine substituents on a benzene ring. This chemical compound has garnered attention in various fields, particularly in organic synthesis and pharmaceutical applications. It is considered a valuable intermediate for the production of a variety of fine chemicals and active pharmaceutical ingredients (APIs).

The compound's structure consists of a benzene ring with a chloro group at the position 3 and a fluorine atom at the position 2, along with an aldehyde functional group (-CHO) at the 1 position. The presence of both electronegative halogens, chlorine and fluorine, on the aromatic ring significantly influences the reactivity and properties of the compound, making it a useful building block in the synthesis of more complex molecules.

3-Chloro-2-fluorobenzaldehyde is primarily used as an intermediate in the synthesis of pharmaceuticals, agrochemicals, and other specialized chemicals. It can serve as a key precursor in the preparation of various bioactive compounds. For instance, the compound has been employed in the synthesis of pharmaceutical agents that exhibit antimicrobial, anticancer, and anti-inflammatory activities. The unique combination of chlorine and fluorine substituents on the benzene ring imparts distinctive electronic properties to the molecule, which can be exploited in designing compounds with improved bioactivity or selectivity.

In organic synthesis, 3-chloro-2-fluorobenzaldehyde is also used in the preparation of substituted benzene derivatives. These derivatives are essential in the development of materials for various industrial applications, including dyes, pigments, and specialty polymers. The aldehyde group in the compound makes it reactive toward nucleophilic addition reactions, providing opportunities for further functionalization and modification to yield products with specific desired properties.

Another notable application of 3-chloro-2-fluorobenzaldehyde is in the synthesis of heterocyclic compounds. The fluorine and chlorine atoms on the aromatic ring enhance the electrophilic character of the aldehyde group, facilitating its participation in reactions that lead to the formation of heterocycles. These heterocycles can then be used in the development of biologically active substances or novel materials.

Moreover, this chemical has been utilized in the development of fluorescent sensors and other analytical tools. Its ability to form complexes with specific metal ions, due to the electron-withdrawing effects of the halogen substituents, allows it to be incorporated into analytical methods for detecting trace amounts of metal ions in various samples.

The synthesis of 3-chloro-2-fluorobenzaldehyde typically involves halogenation reactions on a benzene ring followed by selective functionalization of the aldehyde group. Various synthetic approaches are available to introduce the chlorine and fluorine atoms in the desired positions, and methods such as electrophilic aromatic substitution or transition-metal-catalyzed reactions are commonly employed.

3-Chloro-2-fluorobenzaldehyde is generally regarded as safe for use in controlled chemical processes, though, as with any reactive aldehyde, appropriate safety precautions should be observed during its handling. The compound’s volatility and reactivity require careful management, particularly in industrial and laboratory settings.

In summary, 3-chloro-2-fluorobenzaldehyde is a versatile chemical intermediate with important applications in pharmaceuticals, organic synthesis, and analytical chemistry. Its unique combination of chlorine and fluorine substituents on the benzene ring imparts desirable reactivity and electronic properties, making it a useful building block in the creation of complex molecules and bioactive compounds. Its contributions to the development of specialized chemicals and materials underline its significance in modern synthetic chemistry.

References

2010. Reactions of 2-thienylmethylidene-6-(2-halophenylmethylidene) cyclohexanones with hydrazine hydrate: Regiodirection and the ratio of formed trans-hexahydroindazoles. Russian Journal of Organic Chemistry, 46(11).
DOI: 10.1134/s1070428010110230

2015. Elvitegravir. Pharmaceutical Substances.
https://pharmaceutical-substances.thieme.com