[684-78-6]  · C4HF6NO3  · N,O-Bis(trifluoroacetyl)hydroxylamine  · (MW 225.05)

(conversion of aldehydes to nitriles1)

Physical Data: mp 62 °C (subl, sealed tube; transition 50 °C);1 mp 40-50 °C.2

Solubility: sol ether, benzene, hot CH2Cl2; insol cold CH2Cl2.

Analysis of Reagent Purity: 19F NMR (d -73.7 (s), -74.5 (s)); IR (1848, 1706 cm-1); elemental analysis.

Preparative Method: addition of Trifluoroacetic Anhydride (2.2 equiv) to Hydroxylamine hydrochloride.

Purification: recrystallized from CH2Cl2.

Handling, Storage, and Precautions: hygroscopic; should be dried in a vacuum desiccator.

Conversion of Aldehydes to Nitriles.

In 1959, Pomeroy and Craig reported a new method for direct conversion of aldehydes to nitriles using pyridine and either trifluoroacetohydroxamic acid or N,O-bis(trifluoroacetyl)hydroxylamine, with the latter reagent providing higher yields of products (eq 1).1 The reagent was prepared by refluxing HONH2.HCl with excess TFAA, followed by removal of volatiles and recrystallization from CH2Cl2. More recently, a modification of this procedure has been reported.2 A mechanism proceeding through a cyclic, four-membered intermediate has been proposed.3

Since its first report, this reagent has been used extensively for the aldehyde to nitrile transformation in several complex substrates. Early examples included steroidal systems and mitomycin derivatives.4 N,O-Bis(trifluoroacetyl)hydroxylamine can also be applied to the conversion of a-formyl ketones to the corresponding ketonitriles (eq 2).5

Other examples have demonstrated the compatibility of N,O-bis(trifluoroacetyl)hydroxylamine with a variety of potentially sensitive functional groups. An optically active cyclobutanecarbaldehyde was converted to the corresponding nitrile with no apparent epimerization.6 a,b-Unsaturated aldehydes attached to thiazine or dihydrothiazine rings are also amenable to conversion into the corresponding a,b-unsaturated nitriles.7 The reaction can be carried out in the presence of ester groups,7,8 as exemplified by an early step in the synthesis of steganacine (eq 3).8 Unsaturated aldehydes at the terminus of conjugated polyene systems have also been successfully converted to nitriles.9 1,3-Dithiane-2-carbaldehyde has been converted into the corresponding cyano-1,3-dithiane (eq 4).10

1. Pomeroy, J. H.; Craig, C. A. JACS 1959, 81, 6340.
2. Middleton, W. J. JOC 1984, 49, 919.
3. Durrell, W. S.; Young, J. A.; Dresdner, R. D. JOC 1963, 28, 831.
4. (a) Pike, J. E. JOC 1964, 29, 3476. (b) Remers, W. A.; Roth, R. H.; Weiss, M. J. JACS 1964, 86, 4612. (c) Allen, G. R., Jr.; Weiss, M. J. JOC 1965, 30, 2904.
5. (a) Kissman, H. M.; Hoffman, A. S.; Weiss, M. J. JOC 1962, 27, 3168. (b) Albright, J. D.; Mitscher, L. A.; Goldman, L. JOC 1963, 28, 38. (c) Saksena, A. K.; Ganguly, A. K. TL 1981, 22, 5227.
6. Berson, J. A.; Dervan, P. B.; Malherbe, R.; Jenkins, J. A. JACS 1976, 98, 5937.
7. (a) Bakasse, M.; Reliquet, A.; Reliquet, F.; Duguay, G.; Quiniou, H. JOC, 1989, 54, 2889. (b) Reliquet, F.; Reliquet, A.; Sharrard, F.; Meslin, J. C.; Quiniou, H. PS 1986, 28, 361.
8. Robin, J.-P.; Dhal, R.; Brown, E. T 1984, 40, 3509.
9. Cuichen, D.; Zhenjie, Y.; Mingqian, J. Scientia Sinica (B) 1982, 25, 1021.
10. Bordwell, F. G.; Drucker, G. E.; Andersen, N. H.; Denniston, A. D. JACS 1986, 108, 7310.

F. G. West & John A. Bender

University of Utah, Salt Lake City, UT, USA

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