(1; R = t-Bu)

[88303-13-3]  · C11H16FNO2S  · N-Fluoro-N-t-butyl-p-toluenesulfonamide  · (MW 245.35) (2; R = exo-norbornyl)

[88303-14-4]  · C16H22FNO2S  · N-Fluoro-N-norbornyl-p-toluenesulfonamide  · (MW 311.46) (3; R = endo-norbornyl)

[88303-15-5]  · C16H22FNO2S  · N-Fluoro-N-t-butyl-p-toluenesulfonamide  · (MW 311.46) (4; R = neopentyl)

[88303-17-7]  · C12H18FNO2S  · N-Fluoro-N-neopentyl-p-toluenesulfonamide  · (MW 259.38)

(reagent for the fluorination of carbanions)

Physical Data: (1) mp 59-62.5 °C; (2) mp 54-60 °C; (3) mp 78-81 °C; (4) mp 58-62.5 °C.

Solubility: sol hexane, ether, THF, toluene.

Form Supplied in: white to light yellow solid.

Analysis of Reagent Purity: TLC, 1H NMR.

Preparative Methods: a solution of the N-alkyl-p-toluenesulfonamide in CFCl3/CHCl3 (1:1) at -78 °C is treated with fluorine (1-5%) in nitrogen2 (description of apparatus3).

Purification: flash column chromatography on silica gel.

Handling, Storage, and Precautions: solid can be stored in glass containers and is stable to moisture but becomes yellow at ambient temperatures over time with no significant change in fluorinating ability observed after several weeks. No significant decomposition was observed after freezer storage for one year. Reagent (4) decomposed with abrupt changes in temperature and pressure when heated above 180 °C in a closed pressure vessel.4 These reagents should be handled in a fume hood.

Fluorination of Carbanions.

Treatment of a broad variety of carbanions with an N-fluoro-N-alkyl-p-toluenesulfonamide results in the transfer of fluorine from nitrogen to carbon. The carbanions can be generated under standard conditions and fluorinated in typical ether or hydrocarbon solvents.

Selection of a particular reagent is dependent upon the basicity of the carbanion and polarity of the solvent. For strongly basic carbanions, b-elimination of HF from reagents (2), (3), and (4) can become a major competing side reaction. Use of a nonpolar solvent or mixed polar/nonpolar system, where possible, can suppress elimination. Alternatively, reagent (1) can be used, although it is more difficult to prepare. The selection of type of base or counterion is generally a matter of convenience. Examples of typical carbanion fluorination reactions are included in Table 1.2,5

In addition, N-[18F]fluoro-N-alkyl-p-toluenesulfonamides have been utilized as radiolabeling agents.6

Related sulfonamide-based fluorinating agents include N-fluoro-N-t-butylbenzenesulfonamide7 and camphor-8 and saccharin-based N-fluorosultams.9 N-Fluoro-N-t-butylbenzenesulfonamide was utilized in the preparation of fluoroalkenes7 and difluoroanthracenes10 and is reported to have solubility advantages over the corresponding tolylsulfonamide at very low temperatures.7 Camphor-based N-fluorosultams were utilized to enantioselectively prepare a-fluoro ketones.8 The N-fluoro saccharin-based sultam has been used in a one-pot procedure in the synthesis of a,a-difluoro ketones.11

While the mechanism of fluorination by N-fluoro-N-alkyl-p-toluenesulfonamides has not been examined directly, studies utilizing the closely related sulfonamide-based saccharin-derived sultam suggest that the pathway involves direct nucleophilic attack on fluorine versus a radical or electron transfer mechanism.12

Following the development of the N-fluoro-N-alkyl-p-toluenesulfonamide reagents, N-fluorosulfonimides were prepared and demonstrated to be stable and effective fluorinating agents themselves. Thus N-fluorotrifluoromethylsulfonimide,13 N-fluorobenzenesulfonimide,14 and N-fluoro-o-benzenedisulfonimide15 have found a number of applications. In addition to carbanions, the sulfonimide-based reagents can also directly fluorinate aromatics. This difference with the sulfonamides has been correlated with the relative potentials of the first one-electron reductions of their N-F bonds.16 Similar increased reactivity has been observed with perfluoro-[N-fluoro-N-(4-pyridyl)]methanesulfonamide.17

1. (a) Wilkinson, J. A. CRV 1992, 92, 505. (b) Purrington, S. T.; Kagen, B. S. CRV 1986, 86, 997. (c) Rozen, S.; Filler, R. T 1985, 41, 1111.
2. (a) Barnette, W. E. JACS 1984, 106, 452. (b) Barnette, W. E. U.S. Patent 4 479 901.
3. (a) Lerman, O.; Rozen, S. JOC 1980, 45, 4122. (b) Rozen, S.; Lerman, O. JOC 1980, 45, 672.
4. Unpublished results, DuPont Engineering Test Center, Explosion Hazards Testing.
5. Chenard, B. L.; Van Zyl, C. M. JOC 1986, 51, 3561.
6. Satyamurthy, N.; Bida, G. T.; Phelps, M. E.; Barrio, J. R. Appl. Radiat. Isot. 1990, 41, 733.
7. Lee, S. H.; Schwartz, J. JACS 1986, 108, 2445.
8. Differding, E.; Lang, R. W. TL 1988, 29, 6087.
9. Differding, E.; Lang, R. W. HCA 1989, 72, 1248.
10. Duerr, B. F.; Chung, Y.-S.; Czarnik, A. W. JOC 1988, 53, 2120.
11. Differding, E.; Rüegg, G. M.; Lang, R. W. TL 1991, 32, 1779.
12. (a) Differding, J. E.; Rüegg, G. M. TL 1991, 32, 3815. (b) Differding, E.; Wehrli, M. TL 1991, 32, 3819.
13. Singh, S.; Des Marteau, D. D.; Zuberi, S. S.; Witz, M.; Huang, H.-N. JACS 1987, 109, 7194.
14. Differding, E.; Ofner, H. SL 1991, 187.
15. Davis, F. A.; Han, W. TL 1992, 33, 1153.
16. (a) Gilicinski, A. G.; Pez, G. P.; Syvret, R. G.; Lal, G. S. JFC 1992, 59, 157. (b) Differding, E.; Bersier, P. M. T 1992, 48, 1595.
17. Banks, R. E.; Khazaei, A. JFC 1990, 46, 297.

William E. Barnette

DuPont Agricultural Products, Wilmington, DE, USA

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