6,8-Difluoro-2-tetralone
[CAS# 843644-23-5]

Identification

• Classification: Organic raw materials >> Ketone compound
• Name: 6,8-Difluoro-2-tetralone
• Synonyms: 6,8-Difluoro-3,4-dihydro-2(1H)-naphthalenone
• Molecular Formula: C₁₀H₈F₂O
• Molecular Weight: 182.17
• CAS Registry Number: 843644-23-5
• EC Number: 807-469-8
• SMILES: C1CC2=C(CC1=O)C(=CC(=C2)F)F

Properties

• Density: 1.3±0.1 g/cm³ Calc.^*
• Boiling point: 260.6±40.0 ºC 760 mmHg (Calc.)^*
• Flash point: 99.4±21.5 ºC (Calc.)^*
• Index of refraction: 1.523 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H315-H319-H335
• Precautionary 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
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335

Discovory and Applicatios

6,8-Difluoro-2-tetralone is a difluorinated derivative of tetralone, a bicyclic ketone consisting of a benzene ring fused to a cyclohexanone ring. It has the molecular formula C₁₀H₈F₂O and is characterized by fluorine atoms substituted at the 6- and 8-positions of the aromatic ring. As a member of the tetralone family, this compound serves as an important intermediate in the synthesis of heterocyclic compounds and fluorinated aromatic scaffolds, particularly in pharmaceutical and agrochemical research.

The introduction of fluorine atoms into organic molecules is widely employed in medicinal chemistry because fluorine can profoundly influence electronic distribution, lipophilicity, and metabolic stability without significantly altering steric size. In 6,8-difluoro-2-tetralone, the presence of two fluorine atoms modifies both the electron density of the aromatic system and the reactivity of the adjacent carbonyl group. This structural modification enables regioselective functionalization and has been exploited for preparing bioactive compounds bearing difluorinated benzocyclic frameworks.

The compound can be synthesized by directed electrophilic fluorination or through the use of difluorinated precursors in cyclization reactions that form the tetralone core. One common route involves the fluorination of 2-tetralone or substituted naphthalene derivatives using reagents such as Selectfluor or N-fluorobenzenesulfonimide (NFSI), which provide controlled mono- or difluorination under mild conditions. Alternatively, 6,8-difluoro-2-tetralone can be obtained through Friedel–Crafts acylation of 1,3-difluorobenzene with a cyclic ketone equivalent under Lewis acid catalysis. These methods have been optimized in synthetic organic chemistry for efficient preparation of fluorinated ketones with high positional selectivity.

From a reactivity perspective, the carbonyl group at the 2-position of the tetralone ring is reactive toward nucleophilic addition, condensation, and reduction, allowing it to serve as a versatile building block in multistep syntheses. The difluoro substitution enhances electrophilicity at the carbonyl carbon, facilitating formation of enamines, hydrazones, or oximes, which can be further transformed into more complex heterocycles. The ring system can also undergo catalytic hydrogenation, halogenation, or oxidation reactions that yield substituted tetralins, quinolinones, or naphthalenes, depending on the reaction sequence.

6,8-Difluoro-2-tetralone is also of interest in the synthesis of fluorinated polycyclic aromatic hydrocarbons and functional materials. The difluorotetralone core can act as a key intermediate for constructing fused aromatic systems, such as fluoroquinolines and fluoroisoquinolones, which display improved pharmacokinetic and photophysical properties. In addition, fluorinated tetralones have been investigated as ligands and precursors for the preparation of fluorinated polymers and fine chemicals, where controlled fluorine distribution contributes to enhanced chemical resistance and thermal stability.

Spectroscopic characterization of 6,8-difluoro-2-tetralone typically involves ¹H, ¹³C, and ¹⁹F NMR spectroscopy, which clearly reveal the influence of fluorine atoms on chemical shifts and coupling constants. The carbonyl stretch in infrared spectra appears in the typical range for aryl ketones (around 1680–1700 cm⁻¹), and mass spectrometry confirms the molecular ion peak corresponding to the difluorinated species. The compound is usually handled under standard laboratory conditions and exhibits stability under dry, neutral environments.

Overall, 6,8-difluoro-2-tetralone represents a synthetically useful and electronically distinctive member of the tetralone class. Its dual fluorine substitution offers fine-tuned reactivity and physicochemical behavior, making it valuable for the synthesis of advanced intermediates in medicinal chemistry, materials science, and fluorinated aromatic compound research.

References

O’Hagan D (2008) Understanding organofluorine chemistry. An introduction to the C–F bond. Chemical Society Reviews 37 308–319 DOI: 10.1039/B711844A

Yerien DE, Bonesi S, and Postigo A (2016) Fluorination methods in drug discovery. Organic & Biomolecular Chemistry 14 8398–8427 DOI: 10.1039/C6OB00764C

Gouverneur V and Seppelt K (2015) Introduction: fluorine chemistry. Chemical Reviews 115 563–565 DOI: 10.1021/cr500686k