5'-Fluoro-2'-methoxyacetophenone
[CAS# 445-82-9]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyrimidine compound >> Ketones
• Name: 5'-Fluoro-2'-methoxyacetophenone
• Synonyms: 1-(5-Fluoro-2-methoxyphenyl)ethanone
• Molecular Formula: C₉H₉FO₂
• Molecular Weight: 168.16
• CAS Registry Number: 445-82-9
• EC Number: 622-743-5
• SMILES: CC(=O)C1=C(C=CC(=C1)F)OC

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*, 1.188 g/mL (Expl.)
• Boiling point: 246.8±20.0 ºC 760 mmHg (Calc.)^*
• Flash point: 100.1±16.7 ºC (Calc.)^*
• Index of refraction: 1.488 (Calc.)^*, 1.518 (Expl.)|1.1880
• Refractive index: 1.5186
• Flash point: >110 ºC

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

Safety Data

• Hazard Symbols: GHS05;GHS07 Danger
• Hazard Statements: H302-H315-H318-H319-H335
• Precautionary Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P305+P354+P338-P317-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Serious eye damage	Eye Dam.	1	H318
Specific target organ toxicity - single exposure	STOT SE	3	H335
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319

Discovory and Applicatios

5'-Fluoro-2'-methoxyacetophenone is an aromatic ketone featuring a fluorine atom at the 5' position and a methoxy group at the 2' position on the phenyl ring of acetophenone. Its molecular framework, defined by the presence of electron-donating and electron-withdrawing substituents on a benzene ring, makes it a valuable intermediate in synthetic organic chemistry. The combination of a fluoro substituent and a methoxy group significantly alters the electronic nature of the aromatic ring, offering selective reactivity useful in various chemical transformations.

The discovery and characterization of substituted acetophenones, including 5'-fluoro-2'-methoxyacetophenone, can be traced back to developments in aromatic substitution chemistry during the 20th century. These derivatives have been systematically explored for their synthetic accessibility and the ability to serve as precursors in more complex molecular constructions. Fluoroaromatic compounds in particular gained attention in the mid-20th century with the advent of organofluorine chemistry, which demonstrated the unique properties imparted by the fluorine atom, such as enhanced metabolic stability, lipophilicity, and electron-withdrawing effects.

The methoxy group, being an electron-donating substituent, increases the electron density on the aromatic ring through resonance, whereas the fluorine atom exerts an opposing inductive electron-withdrawing effect. This push-pull interplay between substituents facilitates regioselective transformations, making the compound an attractive synthon in the preparation of heterocycles, halogenated aromatic compounds, or further functionalized acetophenones. The position of the carbonyl group in the acetophenone core provides a reactive site for condensation reactions, nucleophilic additions, or enolate chemistry.

One notable application of 5'-fluoro-2'-methoxyacetophenone is in the pharmaceutical industry, where it can serve as a building block for the synthesis of bioactive molecules. The presence of the fluoro group in drug candidates is often associated with improved pharmacokinetic profiles, such as enhanced oral bioavailability, metabolic resistance, and binding affinity to target biomolecules. Methoxyacetophenone derivatives, in general, have been studied for their potential anti-inflammatory, analgesic, and antimicrobial activities, although specific biological data on 5'-fluoro-2'-methoxyacetophenone itself remains limited to known uses as an intermediate rather than a final therapeutic agent.

In agrochemical research, fluorinated acetophenones are similarly employed as precursors in the development of herbicides, insecticides, and fungicides. Their chemical stability and ability to modulate biological interactions through structural variation make them highly adaptable for use in various lead optimization programs. Substituted acetophenones like this compound allow researchers to introduce specific functional groups while retaining favorable physicochemical properties needed for bioavailability in plants and pest organisms.

From an industrial and materials perspective, 5'-fluoro-2'-methoxyacetophenone may find roles in the production of specialty polymers or advanced materials, particularly where fine-tuning of aromatic substitution patterns is required. The compound's halogenated nature contributes to chemical robustness, which can be desirable in materials exposed to harsh processing conditions or environments. Furthermore, the methoxy group offers a handle for further derivatization, including ether cleavage or transformation into other functionalities.

In analytical chemistry and chemical biology, substituted acetophenones like 5'-fluoro-2'-methoxyacetophenone are also used as reference compounds or reagents in spectroscopic and chromatographic techniques. Their defined aromatic substitution allows for predictable UV absorbance profiles and facilitates their use as markers in reaction monitoring or purity assessments.

Overall, 5'-fluoro-2'-methoxyacetophenone exemplifies a multifunctional aromatic ketone that is synthetically accessible and chemically versatile. Its utility as an intermediate in multiple domains of chemical research and industry underscores the continued importance of halogenated and methoxy-substituted aromatics in modern synthesis and applied sciences.