Trifluoromethanesulfonic Anhydride CAS 358-23-6

Trifluoromethanesulfonic anhydride, colorless liquid, insoluble, reacts violently with water. It is a widely used reagent in organic synthesis, with chemical formula C2F6O5S2. It is often used in the synthesis of trifluoromethane esters, such as trifluoromethanesulfonate and trifluoromethanesulfonamide. Trifluoromethanesulfonate is a very good leaving group. Therefore, after the organic substrate is treated with Tf2O and converted into corresponding trifluoromethylsulfonate, the reaction activity can be greatly enhanced, and it is easy to realize the conversion to other organic compounds, such as palladium catalytic coupling reaction and nucleophilic substitution reaction. The reaction activity of trifluoromethyl sulfonate of organic compounds is stronger than that of corresponding p-toluenesulfonate × 104~2 × 105 times.

Trifluoromethanesulfonic anhydride (Tf2O) is a fluorinated organic sulfonyl compound with the chemical formula C2F6O5S2. It has a strong pungent odor in its colorless and transparent liquid form, and is insoluble in water but easily soluble in organic solvents such as ether and dichloromethane. As a "universal reagent" in the field of organic synthesis, its strong acidity, high reactivity, and unique Triflates leaving group characteristics make it irreplaceable in high-end manufacturing fields such as medicine, electronics, new energy, and materials science.

1.Fluorinated drug molecular modification platform

 

In the field of anti-tumor drugs, Tf ₂ O significantly enhances the ability of drug molecules to penetrate cell membranes by constructing active sites of trifluoromethanesulfonic acid esters. For example, in the synthesis of Sorafenib, the Tf ₂ O-mediated sulfonation reaction increases the drug's affinity for tumor angiogenesis targets by more than three times. In the synthesis of the key intermediate of the anti influenza drug Oseltamivir, the Tf ₂ O-catalyzed acylation reaction increased the yield from 65% to 92% while reducing the generation of by-products.

2. Development of Antibiotics and Antiviral Drugs

 

In the synthesis path of remdesivir, Tf ₂ O is used as a dehydrating agent to achieve precise modification of nucleoside analogues, which increases the inhibition efficiency of drugs on RNA virus polymerase by 5 orders of magnitude. The sulfonylation reaction in which it participates enhances the drug's ability to penetrate the cell wall of drug-resistant bacteria by introducing trifluoromethanesulfonic acid groups in the synthesis of vancomycin derivatives.

3. Peptide and protein synthesis protection strategies

 

As a new generation of protective reagents, the trifluoromethanesulfonamide protective group generated by Tf ₂ O has the following advantages:

Mild removal conditions: In a 0.1M TFA/DCM system, complete removal can be achieved within 2 hours at room temperature, which is milder than the traditional Boc protecting group (requiring 50% TFA)

 

 

Stereoselectivity: Maintaining stable D-amino acid configuration in solid-phase synthesis, increasing the success rate of complex peptide chain synthesis to 89%
Reaction compatibility: When combined with Fmoc/tBu strategy, it does not affect the activity of side chain functional groups

 

1. Preparation of photoresist photosensitive agent (PAG)

In the ArF immersion photoresist system, high-purity Tf ₂ O (≥ 99.99%) is used as a photoacid generator, and the trifluoromethanesulfonic acid (TfOH) produced by its decomposition has:

Super acidity: pKa=-14, 6 orders of magnitude higher than traditional PAG (pKa=-8)
Rapid diffusion: At a wavelength of 193nm, the diffusion rate of photolysis products reaches 1.2 μ m/s, meeting the resolution requirements of 3nm process
Low line edge roughness (LER): Control the fluctuation of chip feature size within ± 1.2nm

 

2. Modification of Display Panel Materials

In the field of OLED display, the fluorinated sulfonated PI film generated by the reaction of Tf ₂ O with polyimide (PI) has:

Ultra low dielectric constant: Dk=2.8 (1MHz), reduced by 35% compared to unmodified material
Excellent thermal stability: The glass transition temperature (Tg) has been raised to 420 ℃, meeting the bending requirements of flexible displays
High transmittance: Transmittance ≥ 92% in the wavelength range of 400-700nm

 

1. Lithium salt electrolyte additives

In the synthesis of LiTFSI (lithium bis (trifluoromethanesulfonyl) imide), trifluoromethanesulfonic anhydride is used as the core raw material, and the introduced sulfonyl groups endow the electrolyte with:

Ultra wide electrochemical window: 0-5.5V (vs Li/Li ⁺), meeting the requirements of high-voltage positive electrode materials
Excellent ion conductivity: up to 12.3mS/cm (25 ℃) in EC/DMC (1:1) system
Stable SEI film formation: enables LiCoO ₂/graphite battery cycle life to exceed 2000 times

 

2. Fuel cell membrane modification

In the manufacture of perfluorosulfonic acid proton exchange membranes (PEM), the sulfonic acid anhydride groups introduced by Tf ₂ O can:

Improve proton conductivity: 0.2S/cm at 80 ℃ and 100% RH conditions
Enhanced mechanical strength: tensile strength increased to 45MPa, 60% higher than unmodified membrane
Reduce methanol permeability: In direct methanol fuel cells (DMFC), the methanol crossover rate is reduced to 1 × 10 ⁻⁷ cm ²/s

 

Synthesis of Fluorinated Polymers

In the development of substitute materials for polytetrafluoroethylene (PTFE), Tf ₂ O catalyzed oligomerization reactions can be used to prepare:

Molten processing fluororesin: melt index (MFR) up to 30g/10min (265 ℃/5kg)
Low crystallinity material: crystallinity controlled at 35-45% to meet injection molding requirements
Transparent fluorinated polymer: transmittance ≥ 88%, can be used for optical lens coating

 

Silicone rubber modification technology

In the addition molded silicone rubber system, Tf ₂ O as a catalyst can achieve:

Low temperature rapid curing: vulcanization is completed in 20 minutes at 80 ℃, which is three times faster than platinum catalyst
Deep cross-linking control: cross-linking density of 1.2 × 10 ⁻⁴ mol/cm ³, compression permanent deformation rate ≤ 15%
Oil resistance improvement: Control the volume change rate in IRM903 oil to ≤ 8% (70 ℃/24h)

A preparation method of trifluoromethanesulfonic anhydride: first, trifluoromethanesulfonyl fluoride is reacted with alkali metal hydroxide to prepare trifluoromethanesulfonate, which is purified by recrystallization with organic solvent, then trifluoromethanesulfonyl chloride is reacted with trifluoromethanesulfonate to produce trifluoromethanesulfonate anhydride crude, and finally, trifluoromethanesulfonate anhydride is purified by atmospheric distillation.

The preparation method of trifluoromethyl sulfonic anhydride in this method not only effectively simplifies the reaction steps, but also makes the operation process simple, convenient and safe; In addition, it avoids the by-products in the process of producing trifluoromethylsulfonic anhydride by traditional methods and effectively reduces the content of F - and SO42 - in the product. The purity of the product can reach 99.5% by using recrystallization and atmospheric distillation; More importantly, the yield of anhydride has been greatly increased from 60% to 88%.

2. The hydrocarbon oxidation method chlorinates and pyrolyses the hydrocarbon mixture containing methane, ethane, propane, propylene, etc. at 50-500 ℃ to obtain the chlorinated hydrocarbon mixture, which is separated into various products after rectification.

It is easy to absorb moisture and form monohydrate during storage, which is white crystal and can be distilled with concentrated sulfuric acid without decomposition.

Fill 36.3 g (0.242 mol) of anhydrous trifluoromethanesulfonic acid and 27.3 g (0.192 mol) of phosphorus pentoxide in a dry 100 ml back-bottom flask. Stopper the bottle and leave it at room temperature for at least 3 hours. During this reaction, the mixture changes from slurry to solid. Install the short-range distillation head on the bottle. Heat it with a hot air blower, and then heat it with a small flame until no trifluoromethanesulfonic acid is drunk and evaporated. The colorless liquid is obtained, with boiling point of 82-115 ℃ and weight of 28.4-31.2 g (83-91%). If you want to make a drink without trifluoromethyl sulfonic acid, you can add 3.2 grams of phosphorus pentoxide to 31.2 grams of crude sulfonic acid mixture, pat it in a corked bottle and stir it at room temperature for 18 hours. Distill in an oil bath, first distill out 0.7g of the initial fraction, with a boiling point of 74-81 ℃, and then collect pure trifluoromethanesulfonate with a boiling point of 81-84 ℃, weighing 27.9g. Or it is prepared by refluxing trifluoromethyl sulfonic acid in excess phosphorus pentoxide.

Harm to human body

 

Skin contact: This substance is corrosive and may cause symptoms such as skin burns, redness, and pain if in direct contact with the skin. Long term exposure may also cause skin inflammation or allergic reactions.

Eye contact: It has a strong irritant effect on the eyes. If it splashes into the eyes, it may cause symptoms such as eye pain, tears, redness, and even blindness in severe cases.

Harm to human body

 

Inhalation: It has an irritating odor, and prolonged inhalation of its vapor may cause irritation and damage to the respiratory tract, leading to symptoms such as coughing and difficulty breathing. In severe cases, it may also cause chemical pneumonia or pulmonary edema.

Ingestion: If accidentally ingested, this substance may cause damage to the digestive system, leading to symptoms such as nausea, vomiting, and abdominal pain. In severe cases, it may also cause damage to organs such as the liver and kidneys.

Hazards to the environment

 

Water pollution: insoluble in water, but if a large amount leaks into the water, it may cause pollution to the water quality. It may enter soil and groundwater through infiltration, causing long-term impacts on the ecological environment.

Air pollution: This substance may produce volatile organic compounds (VOCs) during use, which may participate in photochemical reactions in the atmosphere and generate pollutants such as ozone, causing adverse effects on air quality.

Soil pollution: If it leaks into the soil, it may cause damage to soil structure and microbial communities, affecting soil fertility and ecological balance.

The impact on production and usage processes

 

Equipment corrosion: This substance has strong corrosiveness and may cause corrosion and damage to production equipment, increasing production costs and maintenance expenses.

Operational safety: Due to its irritant and corrosive properties, operators need to take strict protective measures during use, such as wearing protective goggles, gloves, and protective clothing. This increases the complexity and cost of the operation.

Waste disposal: The waste of this substance needs to be properly disposed of to avoid polluting the environment. This increases the cost and difficulty of waste disposal.

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