CAS No.: 333-27-7
EINECS No.: 206-371-7
Chemical Formula: C₂H₃F₃O₃S（CF₃SO₂OCH₃）
Molecular Weight: 164.1
InChI InChI=1S/C₂H₃F₃O₃S/c1-8-9(6,7)2(3,4)5/h1H3
Density 1.45 g/mL at 25°C (lit.)
Boiling Point 94–99 °C (lit.) / 96.5 °C at 760 mmHg
Flash Point 38 °C (101 °F)
Water Solubility Insoluble / Slightly soluble
Vapor Pressure 49.7 mmHg at 25°C
Refractive Index n²⁰/D 1.326 (lit.)
Storage Conditions 2–8°C, sealed and stored in a dry place under inert gas (such as nitrogen/argon) protection
Sensitivity Sensitive to air; hygroscopic; sensitive to moisture; volatile
Appearance Liquid
Specific Gravity 1.45
Color Colorless to pale yellow transparent liquid
BRN 774772
MDL Number MFCD00000409 Hazard Symbols: C (Corrosive); T (Toxic)
Risk Terms (R): R10 (Flammable); R34 (Causes burns); R20/21/22 (Harmful if inhaled, comes into contact with skin or is ingested)
Safety Terms (S): S16 (Keep away from fire); S26 (If contact with eyes, immediately flush with plenty of water and seek medical attention); S36/37/39 (Wear protective clothing, gloves and safety glasses/face shield); S45 (In case of accident or discomfort, seek medical attention immediately and carry product container label)
HS Code: 29049020
II. Properties
Methyl trifluoromethanesulfonate (MeOTf) is a super-strong methylating agent. Its reactivity is approximately 10⁴ times higher than traditional methylating agents (such as iodomethane and dimethyl sulfate), second only to the fluoromethane-antimony pentafluoride superacid system. The trifluoromethanesulfonyl group (–SO₂CF₃) in this compound exhibits a strong electron-withdrawing effect, significantly enhancing the positive charge on the methyl carbon and thus endowing it with excellent electrophilic substitution ability.
This reagent is a colorless to pale yellow transparent liquid at room temperature. It is hygroscopic and volatile, extremely sensitive to air and moisture, and readily hydrolyzes in water to form trifluoromethanesulfonic acid and methanol. Therefore, storage and handling must be carried out under strictly anhydrous and oxygen-free conditions. It has a moderate boiling point (approximately 96°C) and a flash point of 38°C, classifying it as a flammable liquid. During handling, it must be kept away from fire sources and anti-static measures must be taken.
III. Applications Methyl trifluoromethanesulfonate is an irreplaceable high-end methylating reagent in organic synthesis and pharmaceutical chemical industries. Its main applications include:
O-methylation reactions: Widely used for the selective methylation or hydroxyl protection of phenols, alcohols (including sensitive primary/secondary alcohols), carboxylic acids, and sugars. The reaction conditions are mild, the yield is high, and it effectively avoids dehydration or eliminates side reactions in traditional methods.
N-Methylation: Highly efficient for the N-methylation of amines, amides, and heterocyclic compounds (such as indole, piperidine, imidazole, pyrrole, and quinolones), exhibiting superior selectivity compared to iodomethane and dimethyl sulfate, and less prone to over-alkylation to form quaternary ammonium salts.
S-Methylation: Used for the methylation of sulfur-containing compounds such as thiols and thioethers.
Pharmaceutical Intermediate Synthesis: A key monomethylating agent used in the construction of complex molecules such as anticancer drugs (e.g., paclitaxel intermediates), antibiotics, peptides, and alkaloids.
Radiochemistry and PET Imaging: Its ¹¹C-labeled derivative ([¹¹C]MeOTf) is a core methylating agent for the preparation of positron emission tomography (PET) tracers, used in neuroimaging and tumor diagnostic research.
Catalysis and Materials Science: A highly efficient methyl source in cross-coupling reactions such as Suzuki coupling, and also used for the structural modification of functional material molecules.
IV. Preparation Methods The main routes for the industrial and laboratory preparation of methyl trifluoromethanesulfonate are as follows:
Method 1: Reaction of Trifluoromethanesulfonic Acid with Dimethyl Sulfate (Classical Method)
Trifluoromethanesulfonic acid and dimethyl sulfate react in stoichiometric amounts in an all-glass reactor. The reaction product is dried in anhydrous potassium carbonate (K₂CO₃), purified by distillation, and the fraction collected at approximately 96°C yields a high-purity product.
Reaction Equation:
CF₃SO₂OH + (CH₃O)₂SO₂ → CF₃SO₂OCH₃ + CH₃OSO₂OH
Method 2: Salt Formation-Alkylation Method
Trifluoromethanesulfonic acid first reacts with potassium carbonate to form potassium trifluoromethanesulfonate. This potassium trifluoromethanesulfonate then undergoes a methylation reaction with dimethyl sulfate in DMF or DMSO solvent. After the reaction is complete, the product is obtained by adding water to separate the layers, washing with water, and distilling under reduced pressure.
Method 3: Direct Esterification Method
Trifluoromethanesulfonic acid is directly esterified with anhydrous methanol in the presence of a dehydrating agent, followed by distillation to remove water.
Method 4: Anhydride Method (High Yield Method)
Trimethyl orthoformate is slowly added dropwise to trifluoromethanesulfonic acid anhydride under ice bath conditions. The mixture is heated to 25°C and reacted for approximately 15 minutes (the reaction progress can be monitored using NMR). After the reaction is complete, the product is directly distilled under reduced pressure to obtain a colorless liquid product with a yield of up to 99%. V. Safety Information Methyl trifluoromethanesulfonate is a highly toxic, corrosive, and flammable hazardous chemical. Strict adherence to laboratory and industrial safety regulations is mandatory during handling:
GHS Hazard Classes: Acute toxicity (Inhalation Class 1; Skin Contact Class 3; Oral Contact Class 3); Skin Corrosion/Irritation Class 1B; Severe Eye Damage Class 1; Flammable Liquid Class 3
Main Hazardous Characteristics: Highly toxic, highly corrosive, flammable, volatile, sensitive to moisture
Health Hazards: Toxic if inhaled, comes into contact with skin, or is ingested; can cause severe skin burns and eye damage; vapors irritate the respiratory tract.
First Aid Measures: Inhalation: Immediately move to fresh air, keep the airway open, provide artificial respiration or oxygen if necessary, and seek immediate medical attention.
Skin Contact: Immediately remove contaminated clothing and wash with plenty of soap and water for at least 15 minutes. Seek immediate medical attention.
Eye Contact: Immediately flush with plenty of running water for at least 15 minutes, lifting the upper and lower eyelids occasionally. Do not rub eyes. Seek immediate medical attention.
Ingestion: Do not induce vomiting. If conscious, drink milk or water to dilute the ingested substance. Seek immediate medical attention.
Protective Measures: Operate in a high-efficiency fume hood; wear a gas mask or positive pressure breathing apparatus, chemical-resistant gloves, protective eyewear/face shield, and corrosion-resistant protective clothing; the work area should be equipped with eyewash stations and safety showers.
Storage Requirements: Store in a cool (2–8°C), dry, well-ventilated dedicated warehouse; keep away from sources of ignition, heat, and oxidizers; containers must be tightly sealed, and storage under an inert gas (nitrogen/argon) atmosphere is recommended; opened containers must be carefully resealed and kept upright to prevent leakage.
Transport Information: UN Number: UN 2920; Packing Group: PG II / III; Transport Name: Corrosive liquid, flammable; Hazard Class: Class 3.2 (flammable liquid) / Class 8 (corrosive substance); Spill Handling: Immediately evacuate personnel from the spill area to a safe area and eliminate ignition sources. Wearing full protective gear, absorb the waste using inert absorbent materials (such as sand or vermiculite), collect it in a sealed container, and treat it as hazardous waste. Direct rinsing with water is prohibited (to prevent hydrolysis and the generation of corrosive acids).
Waste Disposal: In accordance with local environmental regulations, hand it over to a qualified hazardous waste treatment unit for incineration or other compliant disposal.
VI. Our Company’s Production Advantages and Capacity
As a professional R&D and production enterprise of methyl trifluoromethanesulfonate, our company possesses the following core competitive advantages in this product field:
1. Leading Technology and Mature Process
Proprietary intellectual property synthesis process: Utilizing an optimized anhydride-ester exchange route, the reaction conditions are mild, with high selectivity, few byproducts, and a crude product purity exceeding 98%.
Strict Anhydrous and Oxygen-Free Control: The entire process employs inert gas protection and a closed production system, eliminating product hydrolysis and deterioration from the source and ensuring batch stability.
2. Large-Scale Production Capacity and Supply Guarantee
Annual Production Capacity: Currently, we have an industrial production capacity of 50 tons of methyl trifluoromethanesulfonate per year, which can be rapidly expanded to 100 tons/year based on market demand.
Flexible Packaging Specifications: We offer a full range of packaging options from 1g, 5g, 10g, 100g, 1kg, 5kg to 25kg/drum, supporting customized gram-level research packaging and ton-level industrial packaging.
Inventory and Delivery: We maintain a safety stock of standard specifications. Domestic orders can be delivered within 3-7 working days; international orders support dangerous goods packaging certificates and legal transportation.
3. Quality System and Compliance Certification
We are ISO 9001 quality management system certified, and our production processes strictly adhere to standard operating procedures (SOPs).
We can provide a complete set of technical documents, including COA (Certificate of Analysis), MSDS (Material Safety Data Sheet), HNMR/MS spectra, and residual solvent test reports.
For samples, COA/MSDS documents, or to discuss cooperation, please feel free to contact us.
Post time: May-19-2026
