SHORT PAPER
A Practical Method for the Preparation of Nitriles
65
References
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IICT Communication No. 4047.
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rations; Academic Press:San Diego, 1983; Chap. 17.
(2) Reisner, D.B.; Coring, E.C. Org. Synth. Coll. Vol. IV, 1963,
144.
Scheme 2
(3) Krynitsy, J.A.; Carhart, H.W. Org. Synth. Coll. Vol. IV, 1963,
436.
(4) Kanaoka, Y.; Kuga, T.; Tanizawa, K. Chem. Pharm. Bull.
1970, 18, 397.
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dron Lett. 1973, 2121.
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(12) McElvain, S. M.; Clarke, R. L. J. Am. Chem. Soc. 1947, 69,
2657.
A proposed reaction mechanism is shown in Scheme 2. It
is noteworthy that both acid-sensitive and base-sensitive
groups were completely unaffected because of the mild
reaction conditions. Neither racemization of the α-bearing
carbon16 nor â-elimination of the nitrile groups were ob-
served. In addition, it appears that electron-withdrawing
or -donating groups do not significantly affect the rate of
reaction.
In summary, the short reaction period, the simple workup,
the good yield, and the fairly mild conditions demonstrate
the usefulness and the versatility of this synthetic method.
This method therefore offers an alternative to the well
documented dehydration of carboxamides. The dehydra-
tion of other functional groups such as urea and carbamate
will be reported in due course.
(13) Correia, J. Synthesis 1994, 1127.
(14) Martinez, A. G. ; Subramanian, L.R.; Hanack, M. In Encyclo-
pedia of Reagents for Organic Synthesis, Paquette, L.A., Ed.;
Wiley: Chichester; 1995, pp 5146Ð5152.
(15) Hendrickson, J. B.; Giga, A.; Wareing, J. J. Am. Chem. Soc.
1974, 96, 2275.
(16) The optical rotation of the product 2g indicated that no race-
mization had occurred during the transformation process,
which was confirmed by comparison with the amine hydro-
chloride salt; [a]D +29.5 (c = 1.0, H2O);Lit.17 [a]D +33.0 (c =
1.001, H2O).
Conversion of Primary Amides to Nitriles 1aÐk; General Proce-
dure
Trifluoromethanesulfonic anhydride (310 mg, 1.1 mmol) was add-
ed dropwise to a stirred ice-cooled solution (or suspension) of the
amide (1.0 mmol) in anhyd CH2Cl2 (10 mL) and anhyd Et3N
(202 mg, 2.0 mmol) at such a rate that the temperature was kept be-
low 5¡C. The mixture was allowed to warm to r.t. for the specified
time (Table), quenched with H2O (5 mL) and extracted with CH2Cl2
(2 ¥ 15 mL). The combined organic phases were washed with brine,
dried (Na2SO4) and the solvent was removed in vacuo to afford the
crude product which was purified by column chromatography on
silica gel. Pure nitriles were obtained in 84Ð95% yields (Table).
(17) Effenberger, F.; Kremser, A.; Stelzer, U. Tetrahedron Asymm.
1996, 7, 607.
(18) Aldrich Catalogue Handbook of Fine Chemicals 1996Ð1997.
(19) Lancaster Catalogue Hand Book of Fine Chemicals 1997Ð
1999.
Synthesis 1999, No. 1, 64Ð65 ISSN 0039-7881 © Thieme Stuttgart · New York