2,2-Difluoroethyl tosylate
[CAS# 135206-84-7]

Identification

• Classification: Chemical reagent >> Organic reagent >> Tosylate
• Name: 2,2-Difluoroethyl tosylate
• Synonyms: 2,2-Difluoroethyl 4-methylbenzenesulfonate
• Molecular Formula: C₉H₁₀F₂O₃S
• Molecular Weight: 236.24
• CAS Registry Number: 135206-84-7
• EC Number: 809-947-1
• SMILES: CC1=CC=C(C=C1)S(=O)(=O)OCC(F)F

Properties

• Solubility: Very slightly soluble (0.54 g/L) (25 °C), Calc.^*
• Density: 1.300±0.06 g/cm³ (20 °C 760 Torr), Calc.^*
• Boiling point: 335.0±32.0 °C 760 mmHg (Calc.)^*
• Flash point: 156.4±25.1 °C (Calc.)^*
• Index of refraction: 1.478 (Calc.)^*

^* 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

• Transport Information: UN 1307 3 / PGIII

Discovery and Applications

2,2-Difluoroethyl tosylate is an organofluorine compound that has been prepared and studied as part of the broader development of fluorinated building blocks for organic synthesis. Its structure consists of a 2,2-difluoroethyl group bonded to a tosylate leaving group, making it a useful electrophile in nucleophilic substitution reactions. The discovery of this compound can be traced to efforts in the second half of the twentieth century to design stable but reactive intermediates for introducing fluorinated motifs into more complex molecules. Fluorine chemistry advanced rapidly during this time, as researchers realized the profound influence of fluorine atoms on chemical reactivity, metabolic stability, and biological interactions. The 2,2-difluoroethyl fragment was of particular interest because it provides a balance between stability and reactivity, with the difluoromethylene unit offering distinctive electronic effects. The tosylate functionality, long used as an efficient leaving group in organic reactions, was combined with this difluorinated moiety to create a reagent suitable for a variety of transformations.

Applications of 2,2-difluoroethyl tosylate have been reported in the synthesis of pharmaceuticals, agrochemicals, and fluorinated materials. One of its principal uses is as a precursor for 2,2-difluoroethyl derivatives of heterocycles and aromatic compounds. Through nucleophilic substitution, the tosylate group can be displaced by oxygen, nitrogen, sulfur, or carbon nucleophiles, allowing the incorporation of the difluoroethyl fragment into a wide range of molecular scaffolds. This makes the compound valuable in medicinal chemistry, where the difluoroethyl group can act as a bioisostere for hydroxyl, thiol, or methyl groups, often improving metabolic stability or modulating biological activity. For example, introducing a difluoroethyl substituent into an active pharmaceutical ingredient can slow oxidative metabolism, thereby prolonging its half-life in vivo. Such strategies are common in the design of enzyme inhibitors and receptor ligands.

In agrochemical research, 2,2-difluoroethyl tosylate has been used as a starting material for the synthesis of herbicides and fungicides that incorporate difluoroalkyl side chains. These substituents can improve lipophilicity and enhance the penetration of compounds through plant cuticles, thereby increasing biological effectiveness. The compound also provides access to intermediates that are further elaborated into fluorinated carboxylic acids, amides, and alcohols, many of which serve as structural motifs in crop protection agents.

Beyond pharmaceutical and agrochemical applications, 2,2-difluoroethyl tosylate has also been investigated in the preparation of specialty fluorinated materials. The difluoroethyl group can impart resistance to chemical and thermal degradation when incorporated into polymers or surface-active agents. This makes it a useful building block for fluorinated surfactants, coatings, and fine chemicals where durability and stability are required.

The discovery and development of 2,2-difluoroethyl tosylate represent a part of the larger story of fluorine in chemistry. As chemists sought methods to harness the unique properties of fluorine atoms, the synthesis of reagents like this one provided practical tools for modifying molecular frameworks. Its role as an efficient electrophile and difluoroethyl source continues to make it relevant in synthetic organic chemistry, and its applications across pharmaceuticals, agrochemicals, and materials science highlight its versatility as a functional intermediate.

References

2023. An electrolyte, secondary battery and electrical equipment. Chinese Patent, CN-117199523-A.
Priority Date: 2023-09-07

2023. Electrolyte containing overcharge-preventing additive and lithium ion battery. Chinese Patent, CN-116231075-A.
Priority Date: 2022-09-06

2023. Antiviral heterocyclic compounds. World Intellectual Property Organization, WO-2023200441-A1.
Priority Date: 2022-04-13