[357-83-5]  · C6H11ClF3N  · N,N-Diethyl-2-chloro-1,1,2-trifluoroethylamine  · (MW 189.61)

(converts alcohols to alkyl fluorides,2 carboxylic acids to acid fluorides;3 used as acylating agent4)

Alternate Names: FAR; CCT; Yarovenko's reagent.

Physical Data: bp 32-33 °C/6 mmHg; d 1.19 g cm-3.

Solubility: sol ether, CH2Cl2, acetonitrile.

Preparative Method: from diethylamine and chlorofluoroethylene (87%).5

Form Supplied in: liquid (97%).

Handling, Storage, and Precautions: store at <0 °C. Use within 4 weeks of delivery. Fluorinating agent; handle with caution in a fume hood. Readily reacts with H2O, alcohols, and amines.

Reactivity Pattern.

N,N-Diethyl-2-chloro-1,1,2-trifluoroethylamine, also known as Yarovenko's reagent,6 is a relatively safe fluorinating agent that is easy to use. The reagent is tolerated by many functional groups including carbon-carbon double and triple bonds, aldehydes, ketones, esters, amides, and nitriles.1 It is quantitatively hydrolyzed to its amide (eq 1).2,7 This illustrates its primary reaction mode: elimination of fluorine a to nitrogen to give an iminium ion.

Reaction with Alcohols and Acids.

Alcohols react with FAR under mild conditions to give the corresponding fluorocarbons with inversion of stereochemistry (SN2 process). Yields and enantioselectivities are comparable with those obtained with phenyltetrafluorophosphorane, N,N-Diethylaminosulfur Trifluoride (DAST) and Potassium Fluoride (eq 2).2 This interconversion works well for primary, secondary, benzylic,8 and bridgehead alcohols (eq 3),9 but gives poor results with a- and b-hydroxy nitriles. DAST is superior in the latter application.10 Cyclic secondary and tertiary alcohols tend to give elimination products.

The a-hydroxycyclopropenone (1) reacts with FAR to give an allenic acyl fluoride that was used to synthesize allenic acid and b-keto ester derivatives (eq 4).11

Fluorination of steroidal homoallylic alcohols with FAR gives a variety of products (cyclopropanes, B-ring expansion), depending on the conditions employed. They are thought to be derived from carbocation intermediates.12 Fluorinated cephalosporin derivatives have been prepared as well.13 The title reagent has also been used to prepare a-chloro-a-fluoroacetates derived from carbohydrates.14

Carboxylic acids can be converted to the acyl fluorides in good yields (eq 5).6,15 Perfluoroaryl acids decarboxylate under the same conditions. FAR has been used in the synthesis of a light-stable rhodopsin.3

Heterocyclic Synthesis and Acylation.

Reaction of FAR with o-aminophenol gives the benzoxazole derivative (2) (eq 6). Benzimidazoles, 4-quinazolones, benzothiazoles, and 1,3-benzodioxoles have also been prepared in this manner.16

Indole has been acylated by FAR under mild conditions using a Lewis acid catalyst (eq 7). Thiophene gives 2-acylated products (52%). Electron-rich aromatics give only the para regioisomer (37-78%).4

Miscellaneous Transformations.

FAR has been used in reactions with isocyanates,17 cyanoacetic ester,18 and organosilicon compounds19 and to make fluoroacetic acids.20 It has also been used to convert benzaldehydes to difluoromethylarenes.21 A reagent that behaves much like FAR has been derived from Et2NCF2CHFCF3 and Et2NCF=CFCF3.22

1. Sharts, C. M.; Sheppard, W. A. OR 1974, 21, 125.
2. Leroy, J.; Hebert, E.; Wakselman, C. JOC 1979, 44, 3406.
3. Van der Steen, R.; Groesbeek, M.; Van Amsterdam, L. J. P.; Lugtenburg, J.; Van Oostrum, J.; De Grip, W. J. RTC 1989, 108, 20.
4. Wakeselman, C.; Tordeux, M. CC 1975, 956.
5. (a) Pruett, R. L.; Barr, J. T.; Rapp, K. E.; Bahner, C. T.; Gibson, J. D.; Lafferty, R. H. JACS 1950, 72, 3646. (b) Rapp, K. E.; Barr, J. T.; Pruett, R. L.; Bahner, C. T.; Gibson, J. D.; Lafferty, R. H. JACS 1952, 74, 749.
6. (a) Yarovenko, N. N.; Raksha, M. A. ZOB 1959, 29, 2159 (CA 1960, 54, 9724h). (b) Yarovenko, N. N.; Raksha, M. A. JGU 1959, 29, 2125.
7. For tetrahydrogibberellic acid derivatives, see: Cross, B. E.; Simpson, I. C. JCS(P1) 1982, 2571.
8. Hamman, S.; Barrelle, M.; Tetaz, F.; Beguin, C. G. JFC 1987, 37, 85.
9. Kopecky, J.; Smejkal, J. CCC 1980, 45, 2971 (CA 1981, 95, 24 348g).
10. Florin, C.; Chantegrel, J.; Charlon, C.; Marsura, A.; Luu-Duc, C. Ann. Pharm. Fr. 1985, 43, 595.
11. (a) Crabbe, P.; Carpino, H.; Velarde, E. CC 1971, 1028. (b) Crabbe, P.; Carpino, H.; Velarde, E. JOC 1973, 38, 1478.
12. (a) Kobayashi, T.; Maeda, M.; Komatsu, H.; Kojima, M. CPB 1982, 30, 3082. (b) Knox, L. H.; Valarde, E.; Berger, S.; Delfín, I.; Grezemkovsky, R.; Cross, A. D. JOC 1965, 30, 4160.
13. Müller, B.; Peter, H.; Schneider, P.; Bickel, H. HCA 1975, 58, 2469.
14. (a) Evelyn, L.; Hall, L. D. Carbohydr. Res. 1976, 47, 285. (b) Wood, K. R.; Fischer, D.; Kent, P. W. JCS(C) 1966, 1994.
15. Fokin, A. V.; Studnev, Yu. N.; Rapkin, A. I.; Sultanbekov, D. A.; Potarina, T. M. IZV 1984, 2, 411 (CA 1984, 100, 209 142a).
16. Takaoka, A.; Iwamoto, K.; Kitazume, T.; Ishikawa, N. JFC 1979, 14, 421.
17. (a) Gertsyuk, M. N.; Dronkina, M. I.; Samarai, L. I. ZOB 1980, 16, 1429 (CA 1981, 94, 15 177c). (b) Gertsyuk, M. N.; Gorbatenko, V. I.; Dronkina, M. I.; Samarai, L. I. ZOB 1979, 15, 1556 (CA 1979, 91, 192 748y).
18. Pasternak, V. I.; Dronkina, M. I.; Kukhar, V. P.; Yagupol'skii, L. M. ZOB 1978, 14, 2493 (CA 1979, 90, 137 372a).
19. Vcelak, J.; Chvalovsky, V. Synth. React. Inorg. Met.-Org. Chem. 1977, 7, 123.
20. Tolman, V. CCC 1977, 42, 2537 (CA 1978, 88, 6300m).
21. Folkin, A. V.; Zimin, V. I.; Studnev, Yu. N.; Sultanbekov, D. A. JGU 1968, 38, 1459.
22. Takaoka, A.; Iwakiri, H.; Ishikawa, N. BCJ 1979, 52, 3377.

Kenneth C. Caster

Union Carbide Corporation, South Charleston, WV, USA

Nikolai S. Zefirov & Sergei A. Lermontov

Moscow State University, Russia

Robert Filler

Illinois Institute of Technology, Chicago, IL, USA

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