(Trifluoromethyl)trimethylsilane (TMSCF3) is a flammable colorless liquid with a boiling point of 54–55 °C, a flash point of –17 °C and density of 0.926 g/mL at 20 °C. It is a trifluoromethylation reagent used in nucleophilic addition reactions of aldehydes and ketones. It may be harmful if inhaled, swallowed, absorbed through skin and may cause respiratory tract, skin and eye irritation. TMSCF3 was firstly synthesized by Rupert in 1984 via the condensation reaction of CF3Br and TMSCl with (Et2N)3P.
Silicon-based fluorinating reagents for the efficient trifluoromethylation of carbonyls and ethylene diamines. Precursors used for metal-mediated trifluoromethylation of aromatic, heteroaromatic, vinyl substrates, etc.
TMSCF3 is versatile reagent for trifluoromethylation, such as transition-metal-catalyzed reaction, miscellaneous trifluoromethylation, and addition to carbonyl and imine groups. These reactions are extremely useful approaches in the pharmaceutical and agrochemical industry, because they enhance metabolic stability (metabolic blocking) and alter the compound properties (liphophilicity, binding selectivity).
(Trifluoromethyl)trimethylsilane is prepared from trimethylsilyl chloride and bromotrifluoromethane in the presence of a phosphorus(III) reagent that serves as a halogen acceptor.
Trimethyl(trifluoromethyl)silane (TMSCF3) is also called as Ruppert-Prakash fluorination reagent. It is extensively used for the synthesis of trifluoromethyl-containing compounds.
reaction type: C-C Bond Formation
(Trifluoromethyl)trimethylsilane is classified as toxic and requires careful handling and safety protocols to minimize human exposure. Prolonged or repeated exposure can lead to various health problems such as skin, eye, and respiratory irritation.
160 g of anhydrous toluene and 19.5 g (0.5 mol) of potassium metal were added to a 1000 mL three-necked flask and the apparatus was protected by argon. The temperature was raised to 55 °C, followed by the dropwise addition of a mixture of 104 g (1 mol) styrene and 161 g (1 mol) hexamethyldisilazane over about 30 minutes. The reaction was maintained for 2 hours until the potassium metal was completely dissolved and then cooled to room temperature to obtain a reaction solution. The reaction solution was cooled to -85 °C and maintained for 20 minutes. 81 g (0.75 mol) of trimethylchlorosilane was slowly added dropwise. Subsequently, trifluoromethane was passed into the reaction system and stopped when 35 g (0.5 mol) of trifluoromethane was passed. The reaction mixture was kept at -85°C for 1 hour and then slowly warmed up to room temperature. The reaction mixture was washed twice with water to ensure that all solids were dissolved and left to stratify. The organic layer was separated and distilled to give a final 64 g (88% yield) of trifluoromethyltrimethylsilane.
Purify it by distilling it from trap to trap in a vacuum of 20mm using a bath at 45o and Dry-ice/Me2CO bath for the trap. The liquid in the trap is then washed with ice cold H2O (3x), the top layer is collected, dried (Na2SO4), and the liquid is decanted and fractionated through a helices-packed column at atmospheric pressure. 1H, 1 3C, 1 9F, and 2 9Si NMR can be used for assessing the purity of fractions. [Ruppert et al. Tetrahedron Lett 25 2195 1984, Krishnamurti et al. J Org Chem 56 984 199, Beilstein 4 IV 3892.]
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[3] Patent: US2014/66640, 2014, A1. Location in patent: Paragraph 0057
[4] Patent: WO2017/223406, 2017, A1. Location in patent: Paragraph 00157; 00159; 00160
