Replacement of Sulfur by Fluorine

Replacement of ketones with fluorine by reaction with sulfur tetrafluoride-hy-drogen fluoride, 471... 

The reaction of acetone with sulfur tetrafluoride, hydrogen fluoride and a catalytic amount of disulfur dichloride gives, instead of 2,2-difluoropropane, polyfluorodipropyl sulfides 8, 9, or disulfide 10 in which the number of fluorine atoms depends on the reaction temperature. The same products are obtained when 2,2-difiuoropropane, a product of the replacement of the carbonyl group of acetone by fluorines, is treated with the same reagent (SF4/HF/S2C12).239... 

Sulfur tetrafluoride [7783-60-0] SF, replaces halogen in haloalkanes, haloalkenes, and aryl chlorides, but is only effective (even at elevated temperatures) in the presence of a Lewis acid catalyst. The reagent is most often used in the replacement of carbonyl oxygen with fluorine (15,16). Aldehydes and ketones react readily, particularly if no alpha-hydrogen atoms are present (eg, benzal fluoride [455-31-2] from benzaldehyde), but acids, esters, acid chlorides, and anhydrides are very sluggish. However, these reactions can be catalyzed by Lewis acids (HP, BF, etc). 

The products resulting from such reactions should, therefore, have analogous names. If KBO2 is a borate, KBS2 is a thioborate and KBF is a fluoroborate. Similarly, the replacement of an oxygen atom by a sulfur atom or two fluorine atoms is understandable. However, the relationship of K2BN2 is less obvious, until one considers the dehydration and deammoniation schemes ... 

Perfluoropmacol reacts with sulfur tetrafluonde in an unconventional way instead of replacement of the hydroxyl groups by fluorine, the substitution of four fluonne atoms in the sulfur tetrafluonde molecule with oxygen occurs to give the corresponding spirosulfurane [J6J] (equation 79)... 

Amino groups bound to sulfur can be replaced by fluorine via diazotization. In contrast to carboxylic acid amides, fluorodediazoniation of aromatic sulfonamides IS readily accomplished to give sulfonyl fluorides in high yields [52, 7S (equation 16) Tetrazotization-fluorination of sulfanilamide can also be effected to give a 38% yield of p-fluorobenzenesulfonyl fluoride [52],... 

Yet a further variation of this theme consists in the replacement of the bridging methylene group by sulfur to give a thiadiazepine as the central ring. The starting thiophene ether (26-3) is obtained by the nucleophilic aromatic displacement of fluorine in nitrobenzene (26-1) by the anion from imidazole-2-thiol (26-2). The nitro... 

The most general and useful application of sulfur tetrafluoride is replacement of carbonyl oxygen and hydroxy groups by fluorine. The reaction has broad scope and is effective with all carbonyl and hydroxy compounds. Alcohols are converted into monofluoro derivatives 1, aldehydes, ketones and quinones into gew-difluoro compounds 2 and 3, and carboxylic acids, acid anhydrides, acid halides and amides into trifluoromethyl compounds 4. 

Secondary and tertiary alcohols substituted with perhalogenated groups, such as 2,2,2-trifluoro-l-(pentafluorophcnyl)cthanol, 2-chloro-2.2-difluoro-l-(pentafluorophenyl)elhanol49 0 and l,l,l,3.3,3-hexafluoro-2-phcnylpropan-2-ols, 1-52 react with sulfur tetrafluoride in a conventional way to give products of the replacement of the hydroxy group by fluorine, la, lb and 2, respectively. 

Reaction of esters of hydroxyalkanoic acids with sulfur tetrafluoride, unless forcing conditions arc applied, generally results in selective replacement of the hydroxy group by fluorine to give almost equimolar mixtures of fluoroalkanoates 3 and alkoxycarbonylalkyl fluorosulfites 4 in high total yield.65... 

The reaction of tertiary formamides with sulfur tetrafluoride in the presence of potassium fluoride leads to replacement of both the carbonyl oxygen and formyl hydrogen atoms by fluorine. The formyl group is directly converted into the trifluoromethyl group to give N-(trifluoromethyl)amines which are isolated in almost quantitative yield (see Section 8.2.10.). Thus, dimethylformamide, diethylformamide, piperidinc-l-carbaldehyde, morpholine-1-carbaldehyde and ethyl(phenyl)formamide were converted into the corresponding A -(tri-fluoromethyl)amines 11.175... 

Conversion of tertiary formamides into A-(trifluoromethyl)amines involves a reduction-oxidation process in which sulfur tetrafluoride is reduced to elemental sulfur.175 Both /V,/V-dial-kyldifluoro(phenyl)methy la mines and A -(trifluoromethyl)amines are mild fluorinating reagents for the replacement of hydroxy groups by fluorine.176... 

Perfluorinated tertiary amides and cyclic imides react cleanly with sulfur tetrafluoride/ hydrogen fluoride at elevated temperatures by replacing the carbonyl oxygen atom by fluorines to give good yields of tertiary perfluoroamines, e.g. formation of 13 and 14.178... 

Treatment of adamantane (2) with sulfur tetrafluoride results in the replacement of one, two or three bridgehead hydrogen atoms by fluorine the degree of fluorination depends on the reaction temperature. When the reaction is conducted in hydrogen fluoride solution, substitution of all four bridgehead hydrogens occurs at relatively low temperature.185... 

Thus, the reaction of 1,4-dioxane with sulfur tetrafluoride and hydrogen fluoride in the presence of small amounts of sulfur chlorides or chlorine (0.3 0.5 %) at 185-220°C results in the replacement of 3-5 hydrogen atoms by fluorine to give mixtures of a polyfluoro-1,4-dioxane 1 or 3 and 2-fluoroethyl-l,2,2,2-tetrafluoroethyl ether (2) in a ratio dependent on the reaction temperature.237 Using technical grade sulfur tetrafluoride without addition of a sulfur chloride or chlorine, this reaction is not reproducible, but when carefully purified sulfur tetrafluoride is used the reaction does not give fluorinated products, instead a tar is formed.237... 

In general, substitution of the activated fluorine by sulfur nucleophiles proceeds smoothly under gentle conditions (Table 1). As fluorine in the ortho position to a nitro group is more activated than one in the para position, in the case of difluoronitrobenzenes a selective elimination of the ortho fluorine is possible by keeping the molar ratio of RS /RF low. The activated fluorine can be successfully replaced not only by alkane- or arenethiols, but also by the sulfide ion. giving access to substituted benzcnethiols, and by benzenesulfinate,14 giving access to... 

Perfluoronaphthalene undergoes multiple fluorine elimination by sulfur nucleophiles under similar conditions.3 Whereas the 2.6-bis(alkylsulfanyl)hexafluoronaphthalenes (alkyl = Me, Et, i-Pr) can be obtained in good yields (< 53%), tetra- and penta-substituted products are accessible in very poor yields. However, moderate yields of hexakis(alkylsulfanyl)-substituted products can be obtained in hexamethylphosphoric triamide, i.e. under conditions suitable for complete replacement of all fluorine atoms.3... 

The reaction of diethyl tartrate with sulfur tetrafluonde at 25 °C results in replacement of one hydroxyl group, whereas at 100 °C, both hydroxyl groups are replaced by fluonne to form a,a -difluorosuccmate [7(52] The stereochemical outcome of the fluorination of tartrate esters is retention of configuration at one of the chiral carbon atoms and inversion of configuration at the second chiral center [163,164, 165] Thus, treatment of dimethyl (+)-L-tartrate with sulfur tetrafluonde gives dimethyl meso-a,a difluorosuccinate as the final product [163, 164], whereas dimethyl meso tartrate is converted into a racemic mixture of D- and L-a,a -difluorosuccinates [765] (equation 80)... 

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