(Trifluoromethyl)trimethylsilane
[CAS# 81290-20-2]

Identification

• Classification: Chemical reagent >> Organic reagent >> Silane
• Name: (Trifluoromethyl)trimethylsilane
• Synonyms: Trimethyl(trifluoromethyl)silane; Ruppert's Reagent; TMS-CF3
• Molecular Formula: C₄H₉F₃Si
• Molecular Weight: 142.20
• CAS Registry Number: 81290-20-2
• EC Number: 617-210-9
• SMILES: C[Si](C)(C)C(F)(F)F

Properties

• Density: 0.969 g/mL
• Boiling Point: 55.8±50.0 °C (760 mmHg), Calc.^*, 49 °C
• Flash Point: -12.5±30.1 °C, Calc.^*, -16 °C

Safety Data

• Hazard Symbols: GHS02;GHS07 Danger
• Risk Statements: H225-H315-H319-H335
• Safety Statements: P210-P233-P240-P241-P242-P243-P261-P264-P264+P265-P271-P280-P302+P352-P303+P361+P353-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P370+P378-P403+P233-P403+P235-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Flammable liquids	Flam. Liq.	2	H225
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
Substances or mixtures which in contact with water emit flammable gases	Water-react.	2	H261

• Transport Information: UN 1993

Discovery and Applications

(Trifluoromethyl)trimethylsilane, commonly abbreviated as TMSCF3, is a reagent used extensively in organic synthesis for the introduction of trifluoromethyl groups into molecules. The trifluoromethyl group (CF3) is a highly electron-withdrawing functional group that significantly alters the chemical and physical properties of compounds, making it an important modification in pharmaceuticals, agrochemicals, and materials science.

The discovery of (Trifluoromethyl)trimethylsilane dates back to the development of fluorination chemistry in the mid-20th century. As researchers explored the impact of fluorinated groups on molecular stability and reactivity, the need for efficient reagents to introduce the trifluoromethyl group became apparent. The unique combination of a trifluoromethyl group and a trimethylsilyl group in TMSCF3 was designed to enhance the reagent’s stability and reactivity, making it suitable for a wide range of reactions. This reagent is a convenient source of CF3 groups and is favored for its mild reaction conditions and ability to be used in metal-catalyzed reactions.

One of the primary applications of (Trifluoromethyl)trimethylsilane is in the trifluoromethylation of organic molecules. Trifluoromethylation reactions are particularly important in pharmaceutical chemistry, where the introduction of a CF3 group can dramatically improve a drug’s bioavailability, metabolic stability, and lipophilicity. The use of TMSCF3 has been pivotal in the development of drugs where fluorinated groups enhance the drug's potency or reduce unwanted side effects. Additionally, TMSCF3 is used to modify agrochemicals to improve their environmental stability and efficacy.

In synthetic chemistry, TMSCF3 has gained recognition as a versatile reagent due to its ability to participate in a wide range of reaction mechanisms. It is commonly employed in reactions with carbonyl compounds, including aldehydes and ketones, to form trifluoromethylated alcohols. These products are useful intermediates in the synthesis of various pharmaceuticals and fine chemicals. The ability of TMSCF3 to engage in both nucleophilic and electrophilic trifluoromethylation reactions further increases its utility in complex organic syntheses.

Another important application of (Trifluoromethyl)trimethylsilane is in material science. The introduction of trifluoromethyl groups into polymer backbones using TMSCF3 can improve the thermal and chemical stability of the resulting materials. These fluorinated polymers find uses in coatings, membranes, and advanced materials with unique properties such as increased resistance to degradation and improved mechanical strength.

Furthermore, TMSCF3 is valuable in the development of trifluoromethylated building blocks that can be used in drug discovery, catalysis, and the creation of functionalized materials. Its stability under normal storage conditions and ease of handling have contributed to its popularity in both academic research and industrial applications.

Overall, (Trifluoromethyl)trimethylsilane plays a significant role in the fields of organic synthesis, pharmaceuticals, and materials science due to its ability to efficiently introduce the trifluoromethyl group into a wide range of molecules. Its discovery has enabled numerous advancements in the creation of fluorinated compounds with enhanced properties.

References

2022. Synthesis of Crystalline CF3‐Rich Perfluoropolyethers from Hexafluoropropylene Oxide and (Trifluoromethyl)Trimethylsilane. Macromolecular Rapid Communications, 43(6).
DOI: 10.1002/marc.202200038

2022. Cu-Catalyzed Dual C-O Bonds Cleavage of Cyclic Ethers with Carboxylic Acids, NaI, and TMSCF3 to Give Iodoalkyl Ester. Organic Letters, 24(13).
DOI: 10.1021/acs.orglett.2c00732

1990. Trifluoromethylation of perfluoroaromatic compounds using trifluoromethyltrimethylsilane in the presence of fluoride ions. Bulletin of the Academy of Sciences of the USSR, Division of chemical science, 39(7).
DOI: 10.1007/bf00957892