ORGANIC
LETTERS
2005
Vol. 7, No. 11
2177-2179
From Azides to Nitriles. A Novel Fast
Transformation Made Possible by BrF3
Revital Sasson and Shlomo Rozen*
School of Chemistry, Raymond and BeVerly Sackler Faculty of Exact Sciences,
Tel-AViV UniVersity, Tel-AViV 69978, Israel
Received March 10, 2005
ABSTRACT
Various alkyl and aryl azides, readily obtained from halides or alcohols, were transformed into the corresponding nitriles using bromine
trifluoride in moderate to good yields. The reaction is general and gives positive results with aliphatic, aromatic, cyclic, and functionalized
azides. It can also be applied to the synthesis of optically active nitriles.
For a long time, nitriles have been recognized as efficient
starting materials for the preparation of amines, ketones,
heterocycles, and other families of compounds.1 Usually, they
can be obtained by dehydration of amides or through
nucleophilic reactions with the cyanide ion. While these
methods are very useful, other methods involving readily
accessible starting materials such as alkyl halides or alcohols
that can be converted to nitriles without carbon chain
elongation are needed. The commonly used syntheses also
employ harsh conditions leading to byproducts derived from
eliminations and rearrangements and, in some cases, to
racemization.
Our experience indicates that like F2, bromine trifluoride,
despite its strong reactivity, can under the appropriate
conditions be a remarkably selective reagent. One of these
conditions that has to be fulfilled calls for the soft acidic
bromine to complex a soft basic atom such as nitrogen or
sulfur in the reactant, bringing the reactive naked fluorine
in the vicinity of the reaction center.5 This enabled us to
synthesize various alkyltrifluoromethyls,6 aryltrifluorometh-
10
yls,7 trifluoromethyl ethers,8 R-trifluoromethyl acids,9 CHF2
moiety, â,â-difluoroacrylates,11 and other families of com-
pounds.12 The basic nitrogen atoms in azides offer such an
anchor, and it was of interest to explore the results of such
coordination between BrF3 and the N3 group. We were
pleased to find that, within a few seconds, BrF3 successfully
Azides, as Professor Sharpless, the 2001 Nobel Laureate,
put it, “make fleeting appearance in organic synthesis”
mainly because of “irrational fear”.2 For more than 50 years,
such fears and prejudice were, and occasionally still are,
responsible for the fact that bromine trifluoride (BrF3) is a
reagent that organic chemists have been avoiding. Recently,
we described a new chemistry of azides transforming them
to nitro compounds with HOF‚CH3CN, a reagent derived
directly from F2.3 We report here the reaction of azides with
(4) BrF3 is commercially available from Air Products, Ozark Fluorine
Specialties, and probably other companies around the world. We prepare
our own BrF3 by passing 0.58 mol of pure fluorine through 0.2 mol of
bromine placed in a copper reactor at 0-10 °C. When no excess of bromine
is present, the BrF3 obtained is an indefinitely stable pale yellow liquid
and has a density of 2.5 with a mp of 7-9 °C; see also: Simons, J. H.
Inorg. Synth. 1950, 3, 184. Stein, L. J. Am. Chem. Soc. 1959, 81, 1269.
(5) (a) Sasson, R.; Rozen, S. Tetrahedron 2005, 60, 1083. (b) Hagooly,
A.; Rozen, S. J. Org. Chem. 2004, 69, 8786.
(6) (a) Hagooly, A.; Ben-David, I.; Rozen, S. J. Org. Chem. 2002, 67,
8430.
(7) Rozen, S.; Mishani, E. J. Chem. Soc., Chem. Commun. 1994, 2081.
(8) Ben-David, I.; Rechavi, D.; Mishani, E.; Rozen, S. J. Fluorine Chem.
1999, 97, 75.
4
BrF3 resulting in quite useful and novel syntheses of a
variety of nitriles without incorporation of of fluorine and
bromine atoms.
* Fax: 972-3-6409293.
(1) Friedrich, K; Wallenfels, K. In The Chemistry of the Cyano Group;
Rappoport, Z., Ed.; Wiely: New York, 1970; Patai Series.
(2) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B.
Angew. Chem., Int. Ed. 2002, 41, 2596.
(9) Hagooly, A.; Rozen, S. Chem. Commun. 2004, 594.
(10) Sasson, R.; Hagooly, A.; Rozen, S. Org. Lett. 2003, 5, 769.
(11) Hagooly, A.; Rozen, S. J. Org. Chem. 2004, 69, 8786.
(12) See, for example: Rozen, S.; Ben-David, I. J. Org. Chem. 2002,
67, 8430.
(3) Rozen, S.; Carmeli, M. J. Am. Chem. Soc. 2003, 125, 8118.
10.1021/ol050523h CCC: $30.25
© 2005 American Chemical Society
Published on Web 04/26/2005