Fluorination by sulfur tetrafluoride

Fluorination by sulfur tetrafluoride produces organofluorine compounds from oxygen-containing organic functional groups using sulfur tetrafluoride. The reaction has broad scope, and SF₄ is an inexpensive reagent. It is however hazardous gas whose handling requires specialized apparatus.^[1][2] Thus, for many laboratory scale fluorinations diethylaminosulfur trifluoride ("DAST") is used instead.^[3]

Carboxylic acids, amides, esters, and carboxylate salts convert to the trifluoromethyl derivatives, although conditions vary widely:

SF₄ + RCO₂H → SO₂ + RCF₃ + HF

For carboxlic acids, the first step gives the acyl fluorides, in keeping with the tendency of SF₄ to fluorinate acidic hydroxyl groups:

SF₄ + RCO₂H → SOF₂ + RC(O)F + HF

Similarly SF₄ converts sulfonic acids to sulfonyl fluorides:

SF₄ + RSO₃H → SOF₂ + RSO₂F + HF

Aldehydes and ketones convert to geminal difluorides:

SF₄ + R₂CO → SF₂O + R₂CF₂

Alcohols convert to alkyl fluorides, although this conversion works best with acidic alcohols, such as fluorinated alcohols:^[4]

SF₄ + R₃COH → SF₂O + R₃CF + HF

The mechanism of fluorination by SF₄ is assumed to resemble chlorination by phosphorus pentachloride.^[1] Hydrogen fluoride, a useful solvent for these reactions, activates SF₄:

SF₄ + HF ⇌ SF+3 + HF−2

Species of the type ROSF₃ are often invoked as intermediates. In the case of aldehydes and ketones, SF4 is thought to initially add across the double bond to give R2CFOSF₃.^[4]

A solution of sulfur tetrafluoride in hydrogen fluoride converts hydroxy-containing amino acids to the fluoro amino acids:^[5]

When vicinal diols are combined with SF₄, difluorination occurs with inversion of configuration at only one of the alcohols. This was demonstrated in the synthesis of meso-difluorosuccinate from (L)-tartrate and the synthesis of (D)- and (L)-difluorosuccinate from meso-tartrate.^[6]

Carbonyl compounds generally react with SF₄ to yield geminal difluorides. Reaction times tend to be on the order of hours and yields are moderate.^[7] Fluorination of lactones can provide heterocyclic fluorides, although ring opening has been observed for γ-butyrolactone. The six-membered lactide does not experience ring opening.^[8]

Fluorination opens epoxides to give either geminal or vicinal difluorides in most cases. Monoarylepoxides give geminal products with migration of the aryl group. Yields are low for sterically hindered di- and trisubstituted epoxides. Epoxides substituted with an ester group give vicinal difluorides via an alkoxysulfur trifluoride intermediate.^[9]

Carboxylic acids react with SF₄ to afford trifluoromethyl compounds:^[10]

C₆H₁₃CO₂H + 2 SF₄ → C₆H₁₃CF₃ + 2 SOF₂ + HF

The formation of the trifluoromethyl derivative sometimes competes with formation of tetrafluoroalkyl ethers, which arise from the reaction between difluoromethyl cation and acyl fluoride.^[11][12]

Sulfur tetrafluoride can be used to fluorinate polymers efficiently. This often has a profound effect on polymer properties—fluorination of polyvinyl alcohol, for instance, improves its resistance to strong acids and bases.^[13]

A prostaglandin bearing a trifluoromethyl group at C-16 is prepared using sulfur tetrafluoride.^[14]

For small scale reactions, SF₄ can be inconvenient since it is a gas and stainless steel reaction vessels are required. Many transformations require elevated temperatures. The reaction generates hydrogen fluoride. These concerns have led to interest in alternative fluorinating reagents.^[1] Selenium tetrafluoride, a liquid at room temperature, behaves similarly to SF₄. Diethylaminosulfur trifluoride (DAST) is a derivative of SF₄ that is easier to handle, albeit more expensive.^[3]