Fluorination by sulfur tetrafluoride

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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]

Contents

Main functional group conversions

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

Mechanism

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]

Examples

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

SF4Scope1.png

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]

SF4Scope2 (cropped).png

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]

SF4Scope3.png

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]

SF4Scope4.png

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]

SF4Synth.png

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]

Related Research Articles

<span class="mw-page-title-main">Hydrofluoric acid</span> Solution of hydrogen fluoride in water

Hydrofluoric acid is a solution of hydrogen fluoride (HF) in water. Solutions of HF are colorless, acidic and highly corrosive. It is used to make most fluorine-containing compounds; examples include the commonly used pharmaceutical antidepressant medication fluoxetine (Prozac) and the material PTFE (Teflon). Elemental fluorine is produced from it. It is commonly used to etch glass and silicon wafers.

<span class="mw-page-title-main">Acyl halide</span> Oxoacid compound with an –OH group replaced by a halogen

In organic chemistry, an acyl halide is a chemical compound derived from an oxoacid by replacing a hydroxyl group with a halide group.

Chlorine trifluoride is an interhalogen compound with the formula ClF3. This colorless, poisonous, corrosive, and extremely reactive gas condenses to a pale-greenish yellow liquid, the form in which it is most often sold. Despite being famous for its extreme oxidation properties and igniting many things, chlorine trifluoride is not combustible itself. The compound is primarily of interest in plasmaless cleaning and etching operations in the semiconductor industry, in nuclear reactor fuel processing, historically as a component in rocket fuels, and various other industrial operations owing to its corrosive nature.

<span class="mw-page-title-main">Thionyl fluoride</span> Chemical compound

Thionyl fluoride is the inorganic compound with the formula SOF
2. This colourless gas is mainly of theoretical interest, but it is a product of the degradation of sulfur hexafluoride, an insulator in electrical equipment. The molecule adopts a distorted pyramidal structure, with Cs symmetry. The S-O and S-F distances are 1.42 and 1.58 Å, respectively. The O-S-F and F-S-F angles are 106.2 and 92.2°, respectively. Thionyl chloride and thionyl bromide have similar structures, although these compounds are liquid at room temperature. Mixed halides are also known, such as SOClF, thionyl chloride fluoride.

<span class="mw-page-title-main">Fluorosulfuric acid</span> Chemical compound

Fluorosulfuric acid (IUPAC name: sulfurofluoridic acid) is the inorganic compound with the chemical formula HSO3F. It is one of the strongest acids commercially available. It is a tetrahedral molecule and is closely related to sulfuric acid, H2SO4, substituting a fluorine atom for one of the hydroxyl groups. It is a colourless liquid, although commercial samples are often yellow.

<span class="mw-page-title-main">Xenon difluoride</span> Chemical compound

Xenon difluoride is a powerful fluorinating agent with the chemical formula XeF
2, and one of the most stable xenon compounds. Like most covalent inorganic fluorides it is moisture-sensitive. It decomposes on contact with water vapor, but is otherwise stable in storage. Xenon difluoride is a dense, colourless crystalline solid.

<span class="mw-page-title-main">Sulfur tetrafluoride</span> Chemical compound

Sulfur tetrafluoride is the chemical compound with the formula SF4. It is a colorless corrosive gas that releases dangerous HF upon exposure to water or moisture. Despite these unwelcome characteristics, this compound is a useful reagent for the preparation of organofluorine compounds, some of which are important in the pharmaceutical and specialty chemical industries.

<span class="mw-page-title-main">Selenium tetrafluoride</span> Chemical compound

Selenium tetrafluoride (SeF4) is an inorganic compound. It is a colourless liquid that reacts readily with water. It can be used as a fluorinating reagent in organic syntheses (fluorination of alcohols, carboxylic acids or carbonyl compounds) and has advantages over sulfur tetrafluoride in that milder conditions can be employed and it is a liquid rather than a gas.

Organofluorine chemistry describes the chemistry of organofluorine compounds, organic compounds that contain a carbon–fluorine bond. Organofluorine compounds find diverse applications ranging from oil and water repellents to pharmaceuticals, refrigerants, and reagents in catalysis. In addition to these applications, some organofluorine compounds are pollutants because of their contributions to ozone depletion, global warming, bioaccumulation, and toxicity. The area of organofluorine chemistry often requires special techniques associated with the handling of fluorinating agents.

In inorganic chemistry, sulfonyl halide groups occur when a sulfonyl functional group is singly bonded to a halogen atom. They have the general formula RSO2X, where X is a halogen. The stability of sulfonyl halides decreases in the order fluorides > chlorides > bromides > iodides, all four types being well known. The sulfonyl chlorides and fluorides are of dominant importance in this series.

<span class="mw-page-title-main">Hypofluorous acid</span> Chemical compound

Hypofluorous acid, chemical formula HOF, is the only known oxyacid of fluorine and the only known oxoacid in which the main atom gains electrons from oxygen to create a negative oxidation state. The oxidation state of the oxygen in hypofluorites is 0. It is also the only hypohalous acid that can be isolated as a solid. HOF is an intermediate in the oxidation of water by fluorine, which produces hydrogen fluoride, oxygen difluoride, hydrogen peroxide, ozone and oxygen. HOF is explosive at room temperature, forming HF and O2:

<span class="mw-page-title-main">Diethylaminosulfur trifluoride</span> Chemical compound

Diethylaminosulfur trifluoride (DAST) is the organosulfur compound with the formula Et2NSF3. This liquid is a fluorinating reagent used for the synthesis of organofluorine compounds. The compound is colourless; older samples assume an orange colour.

Fluorination with aminosulfuranes is a chemical reaction that transforms oxidized organic compounds into organofluorine compounds. Aminosulfuranes selectively exchange hydroxyl groups for fluorine, but are also capable of converting carbonyl groups, halides, silyl ethers, and other functionality into organofluorides.

<span class="mw-page-title-main">Electrophilic fluorination</span>

Electrophilic fluorination is the combination of a carbon-centered nucleophile with an electrophilic source of fluorine to afford organofluorine compounds. Although elemental fluorine and reagents incorporating an oxygen-fluorine bond can be used for this purpose, they have largely been replaced by reagents containing a nitrogen-fluorine bond.

<span class="mw-page-title-main">Olah reagent</span>

The Olah reagent is a nucleophilic fluorinating agent. It consists of a mixture of 70% hydrogen fluoride and 30% pyridine; alcohols react with this reagent to give alkyl fluorides:

<span class="mw-page-title-main">Vanadium pentafluoride</span> Chemical compound

Vanadium(V) fluoride is the inorganic compound with the chemical formula VF5. It is a colorless volatile liquid that freezes near room temperature. It is a highly reactive compound, as indicated by its ability to fluorinate organic substances.

<span class="mw-page-title-main">Thiophosphoryl fluoride</span> Chemical compound

Thiophosphoryl fluoride is an inorganic molecular gas with formula PSF3 containing phosphorus, sulfur and fluorine. It spontaneously ignites in air and burns with a cool flame. The discoverers were able to have flames around their hands without discomfort, and called it "probably one of the coldest flames known". The gas was discovered in 1888.

<span class="mw-page-title-main">Neptunium(VI) fluoride</span> Chemical compound

Neptunium(VI) fluoride (NpF6) is the highest fluoride of neptunium, it is also one of seventeen known binary hexafluorides. It is an orange volatile crystalline solid. It is relatively hard to handle, being very corrosive, volatile and radioactive. Neptunium hexafluoride is stable in dry air but reacts vigorously with water.

Fluorine forms a great variety of chemical compounds, within which it always adopts an oxidation state of −1. With other atoms, fluorine forms either polar covalent bonds or ionic bonds. Most frequently, covalent bonds involving fluorine atoms are single bonds, although at least two examples of a higher order bond exist. Fluoride may act as a bridging ligand between two metals in some complex molecules. Molecules containing fluorine may also exhibit hydrogen bonding. Fluorine's chemistry includes inorganic compounds formed with hydrogen, metals, nonmetals, and even noble gases; as well as a diverse set of organic compounds. For many elements the highest known oxidation state can be achieved in a fluoride. For some elements this is achieved exclusively in a fluoride, for others exclusively in an oxide; and for still others the highest oxidation states of oxides and fluorides are always equal.

<span class="mw-page-title-main">Thiothionyl fluoride</span> Chemical compound

Thiothionyl fluoride is a chemical compound of fluorine and sulfur, with the chemical formula S=SF2. It is an isomer of disulfur difluoride (difluorodisulfane) F−S−S−F.

References

  1. 1 2 3 Smith, Michael B.; March, Jerry (2007), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (6th ed.), New York: Wiley-Interscience, p. 1299, ISBN   978-0-471-72091-1
  2. ↑ Wang, Chia-Lin J. (1985). "Fluorination by Sulfur Tetrafluoride". Organic Reactions. pp. 319–400. doi:10.1002/0471264180.or034.02. ISBN   978-0-471-26418-7.
  3. 1 2 Fauq, Abdul H.; Singh, Rajendra P.; Meshri, Dayal T. (2006). "Diethylaminosulfurtrifluoride". Encyclopedia of Reagents for Organic Synthesis. doi:10.1002/047084289X.rd175.pub2. ISBN   0-471-93623-5.
  4. 1 2 Boswell, G. A.; Ripka, W. C.; Scribner, R. M.; Tullock, C. W. (2011). "Fluorination by Sulfur Tetrafluoride". Organic Reactions. pp. 1–124. doi:10.1002/0471264180.or021.01. ISBN   978-0-471-26418-7.
  5. ↑ Kollonitsch, J.; Marburg, S.; Perkins, Leroy (1975). "Selective Fluorination of Hydroxy Amines and Hydroxy Amino Acids with Sulfur Tetrafluoride in Liquid Hydrogen Fluoride". The Journal of Organic Chemistry. 40 (25): 3808–3809. doi:10.1021/jo00913a900.
  6. ↑ Bell, M.; Hudlicky, M. J. Fluorine Chem.1980, 15, 191.
  7. ↑ Mobbs, H. J. Fluorine Chem.1971, 1, 361.
  8. ↑ Muratov, N.; Burmakov, I.; Kunshenko, V.; Alekseeva, A.; Yagupol'skii, M. J. Org. Chem. USSR (Engl. Transl.)1982, 18, 1220.
  9. ↑ Yagupol'skii, M.; Golikov, I.; Alekseeva, A.; Aleksandrov, M. J. Org. Chem. USSR (Engl. Transl.)1971, 7, 737.
  10. ↑ Hasek, W. R. (1961). "1,1,1-Trifluoroheptane". Organic Syntheses . 41: 104. doi:10.15227/orgsyn.041.0104.
  11. ↑ Dmowski, W.; Kolinski, A. Rocz. Chem.1974, 48, 1697.
  12. ↑ Dmowski, W.; Kolinski, A. Pol. J. Chem.1978, 52, 547.
  13. ↑ Bezsolitsen, P.; Gorbunov, N.; Nazarov, A.; Khardin, P. Vysokomol. Soedin., Ser. A1972, 14, 950 [C.A., 77, 75710e (1972)].
  14. ↑ Holland, G. W.; Jernow, J. L.; Rosen, P. U.S. Pat. 4,256,911 (1981) [C.A., 89, 146500x (1978)].
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